Blood treatment systems and methods

ABSTRACT

Dialysis systems comprising actuators that cooperate to perform dialysis functions and sensors that cooperate to monitor dialysis functions are disclosed. According to one aspect, such a hemodialysis system comprises a user interface model layer, a therapy layer, below the user interface model layer, and a machine layer below the therapy layer. The user interface model layer is configured to manage the state of a graphical user interface and receive inputs from a graphical user interface. The therapy layer is configured to run state machines that generate therapy commands based at least in part on the inputs from the graphical user interface. The machine layer is configured to provide commands for the actuators based on the therapy commands.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/901,926, filed Jun. 15, 2020, which is a continuation of U.S. patentapplication Ser. No. 15/469,065, filed Mar. 24, 2017, now U.S. Pat. No.10,682,450, which is a continuation of U.S. patent application Ser. No.14/313,809, entitled “Blood Treatment Systems and Methods,” filed Jun.24, 2014, now U.S. Pat. No. 9,603,985, which is a continuation of U.S.patent application Ser. No. 13/855,620, entitled “Blood TreatmentSystems and Methods,” filed on Apr. 2, 2013, now abandoned, which is adivisional of U.S. patent application Ser. No. 12/549,285, entitled“Blood Treatment Systems and Methods,” filed on Aug. 27, 2009, now U.S.Pat. No. 8,409,441, which claims the benefit, under 35 U.S.C. § 119(e),of U.S. Provisional Application Ser. No. 61/092,239, entitled “ControlSystem and Methods for Hemodialysis Device,” filed on Aug. 27, 2008,which is hereby incorporated herein by reference in its entirety.

U.S. patent application Ser. No. 12/549,285 also claims priority, as acontinuation-in-part, to U.S. patent application Ser. No. 12/199,452,filed Aug. 27, 2008, entitled “Hemodialysis Systems and Methods,” nowU.S. Pat. No. 8,357,298, which in turn is a continuation-in-part of U.S.patent application Ser. No. 12/072,908, filed Feb. 27, 2008, entitled“Hemodialysis Systems and Methods,” now U.S. Pat. No. 8,246,826, whichclaims the benefit of each of U.S. Provisional Patent Application Ser.No. 60/903,582, filed Feb. 27, 2007, entitled “Hemodialysis System andMethods,” and U.S. Provisional Patent Application Ser. No. 60/904,024,filed Feb. 27, 2007, entitled “Hemodialysis System and Methods.” Each ofthe foregoing applications is hereby incorporated herein by reference inits entirety.

FIELD OF INVENTION

The present invention generally relates to hemodialysis and similardialysis systems, e.g., systems able to treat blood or other bodilyfluids extracorporeally. In certain aspects, the systems include avariety of systems and methods that would make hemodialysis moreefficient, easier, and/or more affordable.

BACKGROUND

Many factors make hemodialysis inefficient, difficult, and expensive.These factors include the complexity of hemodialysis, the safetyconcerns related to hemodialysis, and the very large amount of dialysateneeded for hemodialysis. Moreover, hemodialysis is typically performedin a dialysis center requiring skilled technicians. Therefore anyincrease in the ease and efficiency of the dialysis process could havean impact on treatment cost or patient outcome.

FIG. 1 is a schematic representation of a hemodialysis system. Thesystem 5 includes two flow paths, a blood flow path 10 and a dialysateflow path 20. Blood is drawn from a patient. A blood flow pump 13 causesthe blood to flow around blood flow path 10, drawing the blood from thepatient, causing the blood to pass through the dialyzer 14, andreturning the blood to the patient. Optionally, the blood may passthrough other components, such as a filter and/or an air trap 19, beforereturning to the patient. In addition, in some cases, anticoagulant maybe supplied from an anticoagulant supply 11 via an anticoagulant valve12.

A dialysate pump 15 draws dialysate from a dialysate supply 16 andcauses the dialysate to pass through the dialyzer 14, after which thedialysate can pass through a waste valve 18 and/or return to thedialysate feed via dialysate pump 15. A dialysate valve 17 controls theflow of dialysate from the dialysate supply 16. The dialyzer is a typeof filter having a semi-permeable membrane, and is constructed such thatthe blood from the blood flow circuit flows through tiny tubes and thedialysate solution circulates around the outside of the tubes. Therapyis achieved by the passing of waste molecules (e.g., urea, creatinine,etc.) and water from the blood through the walls of the tubes and intothe dialysate solution. At the end of treatment, the dialysate solutionis discarded.

SUMMARY OF THE INVENTION

The present invention generally relates to hemodialysis and similarextracorporeal blood treatment systems. The subject matter of thepresent invention involves, in some cases, interrelated products,alternative solutions to a particular problem, and/or a plurality ofdifferent uses of one or more systems and/or articles. Although thevarious systems and methods described herein are described in relationto hemodialysis, it should be understood that the various systems andmethod described herein are applicable to other dialysis systems and/orin any extracorporeal system able to treat blood or other bodily fluids,such as hemofiltration, hemodiafiltration, etc.

In one aspect, the system includes four fluid paths: blood; innerdialysate; outer dialysate and dialysate mixing. In some embodiments,these four paths are combined in a single cassette. In otherembodiments, these four paths are each in a respective cassette. Instill other embodiments, two or more fluid paths are included on onecassette.

In one embodiment, there is provided a hemodialysis system having atleast two fluid paths integrated into: 1) a blood flow pump cassette, 2)an inner dialysate cassette; 3) an outer dialysate cassette; and 4) amixing cassette. The cassettes may be fluidly connected one to another.In some embodiments, one or more aspects of these cassettes can becombined into a single cassette.

Also provided, in another embodiment, is a hemodialysis system includinga blood flow path through which untreated blood is drawn from a patientand is passed through a dialyzer and through which treated blood isreturned to the patient. The blood flow path may include at least oneblood flow pump located in a removable cassette. The hemodialysis systemalso can include a first receiving structure for receiving the bloodflow path's cassette, a dialysate flow path through which dialysateflows from a dialysate supply through the dialyzer, a second receivingstructure for receiving the dialysate flow path's cassette, and acontrol fluid path for providing a control fluid from an actuatormechanism to the cassettes for actuating each of the blood flow pump andthe dialysate pump. In some instances, the dialysate flow path caninclude at least one dialysate pump located in a removable cassette.

In yet another embodiment, a hemodialysis system is disclosed. Thehemodialysis system, in this embodiment, includes a blood flow paththrough which untreated blood is drawn from a patient and is passedthrough a dialyzer and through which treated blood is returned to thepatient. The blood flow path may include at least one blood valve. Thehemodialysis system may also include a control fluid path for providinga control fluid from an actuator mechanism to the blood valve foractuating the blood valve, a dialysate mixing system fluidly connectedto the dialyzer (which may include at least one dialyzer valve), and aheating means or a heater for heating the dialysate.

A hemodialysis system is disclosed in yet another embodiment thatincludes a blood flow path through which untreated blood is drawn from apatient and passed through a dialyzer and through which treated blood isreturned to the patient. The blood flow path can include at least oneblood flow pump. The hemodialysis system also can include a dialysateflow path through which dialysate flows from a dialysate supply throughthe dialyzer. The dialysate flow path may include at least one pneumaticpump.

In one aspect, the invention is directed to a hemodialysis system. Inone set of embodiments, the hemodialysis system includes a blood flowpath, a first cassette defining an inner dialysate fluid path, adialyzer in fluid communication with the blood flow path and the innerdialysate fluid path, a second cassette defining an outer dialysatefluid path, and a filter fluidly connecting the first cassette to thesecond cassette.

In another set of embodiments, the hemodialysis system, includes a bloodflow path, an inner dialysate fluid path, a dialyzer in fluidcommunication with the blood flow path and the inner dialysate fluidpath, an outer dialysate fluid path, a filter fluidly connecting theinner dialysate fluid path and the outer dialysate fluid path, a firstdialysate pump for pumping dialysate through the inner dialysate fluidpath, and a second dialysate pump for pumping dialysate through theouter dialysate fluid path, where the second dialysate pump and thefirst dialysate pump are operably connected such that flow through theinner dialysate fluid path is substantially equal to flow through theouter dialysate fluid path.

The hemodialysis system, in yet another set of embodiments, includes ablood flow path through which blood is drawn from a patient and passedthrough a dialyzer, and a dialysate flow path through which dialysateflows from a dialysate supply through the dialyzer. In some cases, thedialysate flow path comprises a balancing cassette which controls theamount of dialysate passing through the dialyzer, a mixing cassettewhich forms dialysate from water, and a directing cassette which passeswater from a water supply to the mixing cassette and passes dialysatefrom the mixing cassette to the balancing cassette.

In still another set of embodiments, the hemodialysis system includes acassette system, comprising a directing cassette, a mixing cassette anda balancing cassette. In some cases, the directing cassette is able todirect water from a water supply to the mixing cassette and directdialysate from the mixing cassette to a balancing cassette, the mixingcassette is able to mix water from the directing cassette with dialysatefrom a dialysate supply precursor to produce a precursor, and thebalancing cassette is able to control the amount of dialysate passingthrough a dialyzer.

In one set of embodiments, the hemodialysis system includes a blood flowpath through which blood is drawn from a patient and passed through adialyzer, the blood flow path including a blood flow pump, a dialysateflow path through which dialysate flows from a dialysate supply throughthe dialyzer, where the dialysate flow path includes a dialysate pump,and a control fluid path through which a control fluid actuates theblood flow pump and the dialysate pump.

The hemodialysis system, in another set of embodiments, comprises ablood flow path through which blood is drawn from a patient and passedthrough a dialyzer; and a dialysate flow path through which dialysateflows from a dialysate supply through the dialyzer. In some cases, thedialysate flow path includes at least one pneumatic pump.

The hemodialysis system, in still another set of embodiments, includes afirst pump comprising a pumping chamber and an actuation chamber, asecond pump comprising a pumping chamber and an actuation chamber, acontrol fluid in fluidic communication with each of the actuationchambers of the first and second pumps, and a controller able topressurize the control fluid to control operation of the first andsecond pumps.

In yet another set of embodiments, the hemodialysis system includes afirst valve comprising a valving chamber and an actuation chamber, asecond valve comprising a valving chamber and an actuation chamber, acontrol fluid in fluidic communication with each of the actuationchambers of the first and second valves, and a controller able topressurize the control fluid to control operation of the first andsecond valves.

In one set of embodiments, the hemodialysis system includes a blood flowpath through which blood is drawn from a patient and passed through adialyzer, a cassette containing at least a portion of the blood flowpath, and a spike integrally formed with the cassette, the spike able toreceive a vial of fluid, the integrally formed spike in fluidiccommunication with the blood flow path within the cassette.

The hemodialysis system, in another set of embodiments, includes a bloodflow path through which untreated blood is drawn from a patient andpassed through a dialyzer, a dialysate flow path through which dialysateflows from a dialysate supply through the dialyzer, the dialyzerpermitting dialysate to pass from the dialysate flow path to the bloodflow path, and a gas supply in fluidic communication with the dialysateflow path so that, when activated, gas from the gas supply causes thedialysate to pass through the dialyzer and urge blood in the blood flowpath back to the patient.

In yet another set of embodiments, the hemodialysis system includes ablood flow path through which untreated blood is drawn from a patientand passed through a dialyzer, a dialysate flow path through whichdialysate flows from a dialysate supply through the dialyzer, thedialyzer permitting dialysate to pass from the dialysate flow path tothe blood flow path, a fluid supply, a chamber in fluid communicationwith the fluid supply and the dialysate fluid path, the chamber having adiaphragm separating fluid of the fluid supply from dialysate of thedialysate flow path, and a pressurizing device for pressurizing thefluid supply to urge the diaphragm against the dialysate in the chamber,so as to cause the dialysate to pass through the dialyzer and urge bloodin the blood flow path back to the patient.

The hemodialysis system, in still another set of embodiments, includes ablood flow path through which untreated blood is drawn from a patientand passed through a dialyzer, a dialysate flow path through whichdialysate flows from a dialysate supply through the dialyzer, thedialysate flow path and the blood flow path being in fluidiccommunication, and a pressure device able to urge dialysate in thedialysate flow path to flow into the blood flow path.

In one set of embodiments, the hemodialysis system includes a firsthousing containing a positive-displacement pump actuated by a controlfluid, a fluid conduit fluidly connecting the positive-displacement pumpwith a control fluid pump, and a second housing containing the controlfluid pump, where the second housing is detachable from the firsthousing.

In another set of embodiments, the hemodialysis system includes ahousing comprising a first compartment and a second compartmentseparated by an insulating wall, the first compartment beingsterilizable at a temperature of at least about 80° C., the secondcompartment containing electronic components that, when the firstcompartment is heated to a temperature of at least about 80° C., are notheated to a temperature of more than 60° C.

The hemodialysis system, in yet another set of embodiments, includes ablood flow path through which untreated blood is drawn from a patientand passed through a dialyzer, the blood flow path including at leastone blood valve; a control fluid path for providing a control fluid froman actuator mechanism to the blood valve for actuating the blood valve;a dialysate mixing system fluidly connected to the dialyzer, includingat least one dialyzer valve; and a heater for heating the dialysate.

Another aspect of the present invention is directed to a valving system.In one set of embodiments, the valving system includes a valve housingcontaining a plurality of valves, at least two of which valves eachcomprises a valving chamber and an actuation chamber, each of the atleast two valves being actuatable by a control fluid in the actuationchamber; a control housing having a plurality of fluid-interface portsfor providing fluid communication with a control fluid from a base unit;and a plurality of tubes extending between the valve housing and thecontrol housing, each tube providing fluid communication between one ofthe fluid-interface ports and at least one of the actuation chambers,such that the base unit can actuate a valve by pressurizing controlfluid in the fluid interface port.

In one set of embodiments, the invention is directed to a valveincluding a first plate; a second plate, the second plate having anindentation on a side facing the first plate, the indentation having agroove defined therein, the groove being open in a direction facing thefirst plate; a third plate, wherein the second plate is located betweenthe first and third plate; and a diaphragm located in the indentationbetween the first plate and the second plate, the diaphragm having arim, the rim being held in the groove. The second plate may include avalve seat arranged so that the diaphragm may be urged by pneumaticpressure to seal the valve seat closed, the groove surrounding the valveseat. In some cases, a valve inlet and a valve outlet are definedbetween the second and third plates. In one embodiment, a passage forproviding pneumatic pressure is defined between the first and secondplates.

Yet another aspect of the present invention is directed to a pumpingsystem. The pumping system, in one set of embodiments, includes a pumphousing containing a plurality of pumps, at least two of which pumpseach includes a pumping chamber and an actuation chamber, each of the atleast two pumps being actuatable by a control fluid in the actuationchamber; a control housing having a plurality of fluid-interface portsfor providing fluid communication with a control fluid from a base unit;and a plurality of tubes extending between the pump housing and thecontrol housing, each tube providing fluid communication between one ofthe fluid-interface ports and at least one of the actuation chambers,such that the base unit can actuate a pump by pressurizing control fluidin the fluid interface port.

The invention is generally directed to a pumping cassette in anotheraspect. In one set of embodiments, the pumping cassette includes atleast one fluid inlet, at least one fluid outlet, a flow path connectingthe at least one fluid inlet and the at least one fluid outlet, and aspike for attaching a vial to said cassette. The spike may be in fluidiccommunication with the flow path in some cases.

In one aspect, the invention is generally directed to a pumping cassettefor balancing flow to and from a target. In one set of embodiments, thepumping cassette includes a cassette inlet, a supply line to the target,a return line from the target, a cassette outlet, a pumping mechanismfor causing fluid to flow from the cassette inlet to the supply line andfrom the return line to the cassette outlet, and a balancing chamber. Insome cases, the pumping mechanism includes a pod pump comprising a rigidcurved wall defining a pumping volume and having an inlet and an outlet,a pump diaphragm mounted within the pumping volume; and an actuationport for connecting the pod pump to a pneumatic actuation system so thatthe diaphragm can be actuated to urge fluid into and out of the pumpingvolume, wherein the pump diaphragm separates the fluid from a gas influid communication with the pneumatic actuation system. In certaininstances, the balancing chamber includes a rigid curved wall defining abalance volume; and a balance diaphragm mounted within the balancevolume, where the balance diaphragm separates the balance volume into asupply side and a return side, each of the supply side and the returnside having an inlet and an outlet. In some cases, fluid from thecassette inlet flows to the supply side inlet, fluid from the supplyside outlet flows to the supply line, fluid from the return line flowsto the return side inlet, and fluid from the return side outlet flows tothe cassette outlet.

In another set of embodiments, the pumping system includes a systeminlet, a supply line to the target, a return line from the target, asystem outlet, a pumping mechanism for causing fluid to flow from thesystem inlet to the supply line and from the return line to the systemoutlet, and a balancing chamber.

In one embodiment, the pumping mechanism includes a pod pump comprisinga rigid spheroid wall defining a pumping volume and having an inlet andan outlet, a pump diaphragm mounted within and to the spheroid wall, anda port for connecting the pod pump to a pneumatic actuation system sothat the diaphragm can be actuated to urge fluid into and out of thepumping volume. In some cases, the pump diaphragm separates the fluidfrom a gas in fluid communication with the pneumatic actuation system;

In certain instances, the balancing chamber includes a rigid spheroidwall defining a balance volume, and a balance diaphragm mounted withinand to the spheroid wall. In one embodiment, the balance diaphragmseparates the balance volume into a supply side and a return side, eachof the supply side and the return side having an inlet and an outlet. Insome cases, fluid from the system inlet flows to the supply side inlet,fluid from the supply side outlet flows to the supply line, fluid fromthe return line flows to the return side inlet, and fluid from thereturn side outlet flows to the system outlet. The pumping mechanism mayalso include valving mechanisms located at each of the inlets andoutlets of the supply side and the return side. The valving mechanismsmay be pneumatically actuated.

Yet another aspect of the invention is directed to a cassette. In oneset of embodiments, the cassette includes a first flow path connecting afirst inlet to a first outlet, a second flow path connecting a secondinlet to a second outlet, a pump able to pump fluid through at least aportion of the second flow path, and at least two balancing chambers,each balancing chamber comprising a rigid vessel containing a diaphragmdividing the rigid vessel into a first compartment and a secondcompartment, the first compartment of each balancing chamber being influidic communication with the first flow path and the secondcompartment being in fluidic communication with the second flow path.

In another set of embodiments, the cassette includes a first flow pathconnecting a first inlet to a first outlet; a second flow pathconnecting a second inlet to a second outlet; a control fluid path; atleast two pumps, each pump comprising a rigid vessel containing adiaphragm dividing the rigid vessel into a first compartment and asecond compartment, the first compartment of each pump being in fluidiccommunication with the control fluid path and the second compartmentbeing in fluidic communication with the second flow path; and abalancing chamber able to balance flow between the first flow path andthe second flow path.

The cassette, in still another set of embodiments, includes a first flowpath connecting a first inlet to a first outlet, a second flow pathconnecting a second inlet to a second outlet, and a rigid vesselcontaining a diaphragm dividing the rigid vessel into a firstcompartment and a second compartment. In some cases, the firstcompartment are in fluidic communication with the first fluid path andthe second compartment being in fluidic communication with the secondflow path.

Still another aspect of the invention is generally directed at a pump.The pump includes, in one set of embodiments, a first rigid component; asecond rigid component, the second rigid component having on a sidefacing the first plate a groove defined therein, the groove being openin a direction facing the first rigid component; and a diaphragm havinga rim, the rim being held in the groove by a friction fit in the groovebut without contact by the first rigid component against the rim. Insome cases, the first and second rigid components define, at leastpartially, a pod-pump chamber divided by the diaphragm into separatechambers, and further define, at least partially, flow paths into thepod-pump chamber, wherein the groove surrounds the pod-pump chamber.

In another set of embodiments, the pump includes a substantiallyspherical vessel containing a flexible diaphragm dividing the rigidvessel into a first compartment and a second compartment, the firstcompartment and the second compartment not in fluidic communication witheach other, whereby movement of the diaphragm due to fluid entering thefirst compartment causes pumping of fluid within the second compartmentto occur.

In another set of embodiments, the pump is a reciprocatingpositive-displacement pump. In one embodiment, the pump includes a rigidchamber wall; a flexible diaphragm attached to the rigid chamber wall,so that the flexible diaphragm and rigid chamber wall define a pumpingchamber; an inlet for directing flow through the rigid chamber wall intothe pumping chamber; an outlet for directing flow through the rigidchamber wall out of the pumping chamber; a rigid limit wall for limitingmovement of the diaphragm and limiting the maximum volume of the pumpingchamber, the flexible diaphragm and the rigid limit wall forming anactuation chamber; a pneumatic actuation system that intermittentlyprovides a control pressure to the actuation chamber. In some cases, thepneumatic actuation system includes an actuation-chamber pressuretransducer for measuring the pressure of the actuation chamber, a gasreservoir having a first pressure, a variable valve mechanism forvariably restricting gas flowing between the actuation chamber and thegas reservoir, and a controller that receives pressure information fromthe actuation-chamber pressure transducer and controls the variablevalve so as to create the control pressure in the actuation chamber, thecontrol pressure being less than the first pressure.

Still another aspect of the invention is directed to a method. Themethod, in one set of embodiments, includes acts of providing a firstpump comprising a pumping chamber and an actuation chamber, and a secondpump comprising a pumping chamber and an actuation chamber, urging acommon fluid into the actuation chambers of each of the first and secondpumps, and pressurizing the common fluid to pump fluids through each ofthe first and second pumps.

In another set of embodiments, the method includes acts of providing afirst valve comprising a valving chamber and an actuation chamber, and asecond valve comprising a valving chamber and an actuation chamber,urging a common fluid into the actuation chambers of each of the firstand second valves, and pressurizing the common fluid to at leastpartially inhibit fluid flow through each of the first and secondvalves.

In yet another set of embodiments, the method is a method for measuringthe clearance of a dialyzer, the dialyzer being located in a blood flowpath, through which untreated blood can be drawn from a patient andpassed through the dialyzer, and in a dialysate flow path, through whichdialysate can flow from a dialysate supply through the dialyzer, theblood flow path being separated from the dialysate flow path bymembranes in the dialyzer. In one embodiment, the method includes actsof urging a liquid through the dialysate flow path to the dialyzer, soas to keep the membranes wet and prevent the flow of a gas through themembranes, urging a gas through the blood flow path to the dialyzer soas to fill the blood flow path in the dialyzer with the gas, measuringthe volume of gas in the dialyzer, and calculating the clearance of thedialyzer based on the volume of gas measured in the dialyzer.

The method, in still another set of embodiments, is a method formeasuring the clearance of a dialyzer. In one embodiment, the methodincludes acts of applying a pressure differential across the dialyzer,measuring the flow rate of the dialyzer, and determining the clearanceof the dialyzer based on the pressure differential and the flow rate.

In yet another set of embodiments, the method is a method for measuringthe clearance of a dialyzer. In one embodiment, the method includes actsof passing water through the dialyzer, measuring the amount of ionscollected by the water after passing through the dialyzer, anddetermining the clearance of the dialyzer based on the amount of ionscollected by the water after passing through the dialyzer. In anotherset of embodiments, the method includes acts of passing water throughthe dialyzer, measuring the conductivity of the water, and determiningthe clearance of the dialyzer based on changes in the conductivity ofthe water.

In one set of embodiments, the method is a method for introducing afluid into blood. The method includes, in one embodiment, acts ofproviding a cassette including an integrally formed spike for receivinga vial of fluid, and a valving mechanism for controlling flow of thefluid from the vial into the cassette, attaching a vial containing thefluid to the spike, pumping blood through the cassette, and introducingthe fluid from the vial into the blood.

In one set of embodiments, the method includes acts of providing ahemodialysis system comprising a blood flow path through which untreatedblood is drawn from a patient and passed through a dialyzer, and adialysate flow path through which dialysate flows from a dialysatesupply through the dialyzer, putting the blood flow path and thedialysate flow path into fluidic communication, and urging dialysatethrough the dialysate flow path to cause blood in the blood flow path topass into the patient.

The method, in another set of embodiments, includes acts of providing ahemodialysis system comprising a blood flow path through which untreatedblood is drawn from a patient and passed through a dialyzer, and adialysate flow path through which dialysate flows from a dialysatesupply through the dialyzer, putting the blood flow path and thedialysate flow path into fluidic communication, and urging a gas intothe dialysate flow path to cause flow of blood in the blood flow path.

The method is a method of performing hemodialysis, in still another setof embodiments. In one embodiment, the method includes acts of providinga blood flow path, through which untreated blood can be drawn from apatient and passed through a dialyzer; providing a dialysate flow path,through which dialysate can flow from a dialysate supply through thedialyzer; providing ingredients for preparing a total volume ofdialysate; providing water for mixing with the dialysate ingredients;mixing a volume of water with a portion of the ingredients so as toprepare a first partial volume of dialysate, the first partial volumebeing less than the total volume; pumping the partial volume ofdialysate through the dialysate flow path and through the dialyzer;pumping blood through the blood flow path and through the dialyzer,while the first partial volume of dialysate is being pumped to thedialyzer; and mixing a volume of water with a portion of the ingredientsso as to prepare a second partial volume of dialysate and storing thesecond partial volume of dialysate within a vessel while the blood andthe first partial volume of dialysate are pumped through the dialyzer.

In another embodiment, the method includes acts of passing blood from apatient and dialysate through a dialyzer contained within a hemodialysissystem at a first rate, and forming dialysate within the hemodialysissystem at a second rate that is substantially different from the firstrate, wherein excess dialysate is stored within a vessel containedwithin the hemodialysis system.

Another aspect of the invention is directed to a hemodialysis systemcomprising a dialysis unit and a user interface unit. The dialysis unitcomprises an automation computer and dialysis equipment. The userinterface unit comprises a user interface computer and a user interface,the user interface being adapted to display information and receiveinputs. The automation computer is configured to receive requests forsafety-critical information from the user interface computer and toaccess the safety-critical information on behalf of the user interfacecomputer. The user interface computer is configured to displayinformation related to a dialysis process via the user interface usingthe safety-critical information.

A further aspect of the invention is directed to a method of managing auser interface in a hemodialysis system. The method comprises receivingan input related to a dialysis process at a user interface associatedwith a user interface computer and, in response to the input,transmitting a request for safety-critical information from the userinterface computer to an automation computer associated with dialysisequipment. The method further comprises accessing the safety-criticalinformation on behalf of the user interface computer and, using thesafety-critical information, displaying information related to thedialysis process via the user interface.

Still another aspect of the invention is directed to a computer storagemedia encoded with instructions that, when executed, perform a method.The method comprising acts of receiving, from a user interfaceassociated with a user interface computer, an input related to adialysis process and, in response to the input, transmitting a requestfor safety-critical information from the user interface computer to anautomation computer associated with dialysis equipment. The methodfurther comprises accessing the safety-critical information on behalf ofthe user interface computer, transmitting the safety-criticalinformation to the user interface computer, accessing screen designinformation stored within the user interface computer and, using thesafety-critical information and the screen design information, causingthe user interface to display information related to the dialysisprocess.

In another aspect, the present invention is directed to a method ofmaking one or more of the embodiments described herein, for example, ahemodialysis system. In another aspect, the present invention isdirected to a method of using one or more of the embodiments describedherein, for example, a hemodialysis system.

In yet another aspect, the invention relates to a control architecturefor such a hemodialysis system comprising a user interface model layer,a therapy layer, below the user interface model layer, and a machinelayer below the therapy layer. The user interface model layer isconfigured to manage the state of a graphical user interface and receiveinputs from a graphical user interface. The therapy layer is configuredto run state machines that generate therapy commands based at least inpart on the inputs from the graphical user interface. The machine layeris configured to provide commands for the actuators based on the therapycommands.

A further aspect of the invention is directed to a method fordisinfecting fluid pathways in a dialysis system. The method comprisesstoring, on at least one storage medium, disinfection parametersincluding a disinfection temperature and a disinfection time. The methodfurther comprises circulating a fluid in the fluid pathways, monitoringa temperature of the fluid at each of a plurality of temperaturesensors, and determining that disinfection of the fluid pathways iscomplete when the temperature of the fluid at each of the plurality oftemperature sensors remains at or above the disinfection temperature forat least the disinfection time.

Another aspect of the invention is directed to at least onecomputer-readable medium encoded with instructions that, when executedon at least one processing unit, perform a method for disinfecting fluidpathways in a dialysis system. The method comprises electronicallyreceiving disinfection parameters including a disinfection temperatureand a disinfection time. The method further comprises controlling aplurality of actuators to circulate a fluid in the fluid pathways,monitoring a temperature of the fluid at each of a plurality oftemperature sensors, and determining whether the temperature of thefluid at each of the plurality of temperature sensors remains at orabove the disinfection temperature for at least the disinfection time.

A further aspect of the invention is directed to a method forcontrolling the administration of an anticoagulant in a dialysis system.The method comprises storing, on at least one storage medium, ananticoagulant protocol comprising a maximum amount of anticoagulant,automatically administering the anticoagulant according to theanticoagulant protocol, and prohibiting the administration of additionalanticoagulant after determining that the maximum amount of anticoagulanthas been administered.

Another aspect of the invention is directed to at least onecomputer-readable medium encoded with instructions that, when executedon at least one processing unit, perform a method for controlling theadministration of an anticoagulant in a dialysis system. The methodcomprises electronically receiving an anticoagulant protocol comprisinga maximum amount of anticoagulant, controlling a plurality of actuatorsto administer the anticoagulant according to the anticoagulant protocol,and prohibiting the administration of additional anticoagulant afterdetermining that the maximum amount of anticoagulant has beenadministered.

A further aspect of the invention is directed to a method fordetermining a fluid level in a dialysate tank of a dialysis system. Themethod comprises tracking a first number of strokes delivering fluid tothe dialysate tank, tracking a second number of strokes withdrawingfluid from the dialysate tank, and determining a fluid level in thedialysate tank based, at least in part, on the first number of strokes,the second number of strokes, and a per-stroke volume.

A further aspect of the invention is directed to a method fordetermining a fluid level in a dialysate tank of a dialysis system. Themethod comprises charging a reference chamber of a known volume to apredetermined pressure and venting the reference chamber to thedialysate tank. The method further comprises, after venting thereference chamber to the dialysate tank, determining a pressure in thedialysate tank. In addition, the method comprises determining a fluidlevel in the dialysate tank based, at least in part, on the determinedpressure in the dialysate tank.

Another aspect of the invention is directed to a method for returningblood to a patient in the event of a power failure condition in adialysis system that uses compressed air to actuate pumps and/or valvesduring a dialysis process, wherein the dialysis system comprises adialyzer having a membrane that separates a blood flow path from adialysate flow path. The method comprises identifying a power failurecondition in a dialysis system. The method further comprises, inresponse to the identification of a power failure condition, releasingcompressed air from a reservoir associated with the dialysis system. Inaddition, the method comprises using the released compressed air,increasing a pressure in the dialysate flow path to cause blood in theblood flow path to return to the patient.

A further aspect of the invention is directed to a method for returningextracorporeal blood to a patient, in an extracorporeal treatmentsystem, using a source of compressed gas in the event of a powerfailure. The extracorporeal treatment system comprises a filter having asemi-permeable membrane that separates a blood flow path from anelectrolyte solution flow path. The compressed gas is in valvedcommunication with an electrolyte solution container, and theelectrolyte solution container is in valved communication with theelectrolyte solution flow path. The method comprises, in response to atermination of electrical power to one or more electrically actuatedvalves that control a distribution of compressed gas or a distributionof electrolyte solution flow in the extracorporeal treatment system,causing one or more first electrically actuated valves to open a firstfluid pathway between the compressed gas and the electrolyte solutioncontainer, causing one or more second electrically actuated valves toopen a second fluid pathway between said electrolyte solution containerand said filter, causing one or more third electrically actuated valvesto close an alternate fluid pathway in said electrolyte solution flowpath if said alternate fluid pathway diverts electrolyte solution awayfrom said filter; and using the compressed gas to increase pressure inthe electrolyte solution flow path to cause blood in the blood flow pathto return to the patient.

Another aspect of the invention is directed to a method for returningextracorporeal blood to a patient, in an extracorporeal treatmentsystem, using a source of compressed gas in the event of a powerfailure. The extracorporeal treatment system comprises a filter having asemi-permeable membrane that separates a blood flow path from anelectrolyte solution flow path. The compressed gas is in valvedcommunication with an electrolyte solution container, and theelectrolyte solution container is in valved communication with theelectrolyte solution flow path. The method comprises, in response to atermination of electrical power to one or more electrically actuatedvalves that control a distribution of compressed gas or a distributionof electrolyte solution flow in the extracorporeal treatment system:causing one or more electrically actuated valves to open a fluid pathwaybetween the compressed gas and the electrolyte solution container, and,using the compressed gas, causing flow of an electrolyte solution fromthe electrolyte solution container through the filter to cause blood inthe blood flow path to return to the patient.

Other advantages and novel features of the present invention will becomeapparent from the following detailed description of various non-limitingembodiments of the invention when considered in conjunction with theaccompanying figures. In cases where the present specification and adocument incorporated by reference include conflicting and/orinconsistent disclosure, the present specification shall control. If twoor more documents incorporated by reference include conflicting and/orinconsistent disclosure with respect to each other, then the documenthaving the later effective date shall control.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting embodiments of the present invention will be described byway of example with reference to the accompanying figures, which areschematic and are not intended to be drawn to scale. In the figures,each identical or nearly identical component illustrated is typicallyrepresented by a single numeral. For purposes of clarity, not everycomponent is labeled in every figure, nor is every component of eachembodiment of the invention shown where illustration is not necessary toallow those of ordinary skill in the art to understand the invention. Inthe figures:

FIG. 1 is a schematic representation of a hemodialysis system;

FIGS. 2A-2B are high-level schematics of various embodiments of adialysis system;

FIGS. 3A-3B are schematics showing an example of a fluid schematic for adialysis system;

FIGS. 4A-4B are schematic representations of various embodiments of ablood flow circuit that may be used in a hemodialysis system;

FIGS. 4C and 4D are perspective and side views, respectively, of the airtrap shown in FIG. 4A;

FIG. 5 is a schematic representation of one embodiment of a balancingcircuit that may be used in a hemodialysis system;

FIG. 6 is a schematic representation of a directing circuit that may beused in a hemodialysis system;

FIGS. 7A-7B are schematic representations of mixing circuits that may beused in a hemodialysis system;

FIGS. 8A-8C are graphical representations of phase relationships;

FIG. 9 is a sectional view of a valve that may be incorporated intoembodiments of the fluid-control cassettes;

FIG. 10 is a sectional view of a pod-pump that may be incorporated intoembodiments of the fluid-control cassettes;

FIGS. 11A-11B are schematic views of various pneumatic control systemfor a pod pump;

FIG. 12 is a graph showing how pressures applied to a pod pump may becontrolled;

FIGS. 13A-13B are graphical representations of occlusion detection;

FIG. 14 is a diagram of one embodiment of a control algorithm;

FIG. 15 is a diagram of one embodiment of the controller's standarddiscrete PI regulator;

FIG. 16 is a schematic representation of a dual-housing cassettearrangement according to one embodiment;

FIGS. 17A-17C are schematics relating to the priming of a portion of asystem, in one embodiment of the invention;

FIGS. 18A-18B illustrate the fluid flow of dialysate from a dialysatetank, through the dialyzer and out to drain in one embodiment of theinvention;

FIG. 19 illustrates emptying of a dialysate tank, in another embodimentof the invention;

FIG. 20 illustrates the purging of the system with air at the end oftreatment according to one embodiment of the invention;

FIGS. 21A-21C illustrate the drawing of air in an anticoagulant pump, instill another embodiment of the invention;

FIGS. 22A-22D illustrate integrity tests according to certainembodiments of the invention;

FIG. 23 illustrates a recirculating flow path, in another embodiment ofthe invention;

FIGS. 24A-24D illustrate the priming of a system with dialysate, in yetanother embodiment of the invention;

FIG. 25 illustrates the priming of an anticoagulant pump, in stillanother embodiment of the invention;

FIGS. 26A-26F illustrate the removal of dialysate from a blood flowcircuit, in one embodiment of the invention;

FIGS. 27A-27C illustrate the delivery of a bolus of anticoagulant to apatient, in another embodiment of the invention;

FIG. 28 illustrates solution infusion, in one embodiment of theinvention;

FIGS. 29A-29B are schematic representations showing how an emergencyrinse-back procedure can be implemented;

FIGS. 30A and 30B are isometric and top views of an outer top plate ofan exemplary embodiment of the cassette;

FIGS. 30C and 30D are isometric and top views of an inner top plate ofan exemplary embodiment of the cassette;

FIG. 30E is a side view of the top plate of an exemplary embodiment ofan cassette;

FIGS. 31A and 31B are isometric and top views of the liquid side of amidplate according to an exemplary embodiment of the cassette;

FIGS. 31C and 31D are isometric and top views of the air side of amidplate according to an exemplary embodiment of the cassette;

FIGS. 32A and 32B are isometric and top views of the inner side of abottom plate according to an exemplary embodiment of the cassette;

FIGS. 32C and 32D are isometric and top views of the outer side of abottom plate according to an exemplary embodiment of the cassette;

FIG. 32E is a side view of a bottom plate according to an exemplaryembodiment of the cassette;

FIG. 33A is a top view of an assembled exemplary embodiment of acassette with a vial attached;

FIG. 33B is a bottom view of an assembled exemplary embodiment of acassette with a vial attached;

FIG. 33C is an exploded view of an assembled exemplary embodiment of acassette with a vial;

FIG. 33D is an exploded view of an assembled exemplary embodiment of acassette with a vial;

FIG. 34A is an isometric bottom view of an exemplary embodiment of themidplate of an exemplary embodiment of the cassette;

FIG. 34B is an isometric top view of the midplate of an exemplaryembodiment of a cassette;

FIG. 34C is an isometric bottom view of an exemplary embodiment of themidplate of a cassette;

FIG. 34D is a side view of an exemplary embodiment of the midplate of acassette;

FIGS. 35A-35B are isometric and top views of an exemplary embodiment ofthe top plate of an exemplary embodiment of the cassette;

FIGS. 35C-35D are isometric views of an exemplary embodiment of the topplate of an exemplary embodiment of the cassette;

FIG. 35E is a side view of an exemplary embodiment of the top plate of acassette;

FIGS. 36A and 36B are isometric bottom views of an exemplary embodimentof the bottom plate of an exemplary embodiment of a cassette;

FIGS. 36C and 36D are isometric top views of an exemplary embodiment ofthe bottom plate of an exemplary embodiment of a cassette;

FIG. 36E is a side view of an exemplary embodiment of the bottom plateof an exemplary embodiment of a cassette;

FIG. 37 is an isometric front view of an exemplary embodiment of theactuation side of the midplate of a cassette with the valves indicatedcorresponding to FIG. 36 ;

FIG. 38A is a view of an exemplary embodiment of the outer top plate ofa cassette;

FIG. 38B is a view of an exemplary embodiment of the inner top plate ofa cassette;

FIG. 38C is a side view of an exemplary embodiment of the top plate of acassette;

FIG. 39A is a view of an exemplary embodiment of the fluid side of themidplate of a cassette;

FIG. 39B is a front view of an exemplary embodiment of the air side ofthe midplate of a cassette;

FIG. 39C is a side view of an exemplary embodiment of the midplate of acassette;

FIG. 40A is a view of an exemplary embodiment of the inner side of thebottom plate of a cassette;

FIG. 40B is a view of an exemplary embodiment of the outer side of thebottom plate of a cassette;

FIG. 40C is a side view of an exemplary embodiment of the midplate of acassette;

FIGS. 41A and 41B are isometric and front views of an exemplaryembodiment of the outer top plate of an exemplary embodiment of acassette;

FIGS. 41C and 41D are isometric and front views of an exemplaryembodiment of the inner top plate of a cassette;

FIG. 41E is a side view of the top plate of an exemplary embodiment of acassette;

FIGS. 42A and 42B are isometric and front views of an exemplaryembodiment of the liquid side of the midplate of a cassette;

FIGS. 42C and 42D are isometric and front views of an exemplaryembodiment of the air side of the midplate of a cassette;

FIG. 42E is a side view of the midplate according to an exemplaryembodiment of a cassette;

FIGS. 43A and 43B are isometric and front views of the inner side of abottom plate according to an exemplary embodiment of a cassette;

FIGS. 43C and 43D are isometric and front views of an exemplaryembodiment of the outer side of the bottom plate of a cassette;

FIG. 43E is a side view of a bottom plate according to an exemplaryembodiment of a cassette;

FIG. 44A is a top view of an assembled exemplary embodiment of acassette;

FIG. 44B is a bottom view of an assembled exemplary embodiment of acassette;

FIG. 44C is an exploded view of an assembled exemplary embodiment of acassette;

FIG. 44D is an exploded view of an assembled exemplary embodiment of acassette;

FIG. 45 shows a cross sectional view of an exemplary embodiment of anassembled cassette;

FIG. 46A is a front view of the assembled exemplary embodiment of thecassette system;

FIG. 46B is an isometric view of the assembled exemplary embodiment ofthe cassette system;

FIG. 46C is an isometric view of the assembled exemplary embodiment ofthe cassette system;

FIG. 46D is an exploded view of the assembled exemplary embodiment ofthe cassette system;

FIG. 46E is an exploded view of the assembled exemplary embodiment ofthe cassette system;

FIG. 47A is an isometric view of an exemplary embodiment of the pod ofthe cassette system;

FIG. 47B is an isometric view of an exemplary embodiment of the pod ofthe cassette system;

FIG. 47C is a side view of an exemplary embodiment of the pod of thecassette system;

FIG. 47D is an isometric view of an exemplary embodiment of one half ofthe pod of the cassette system;

FIG. 47E is an isometric view of an exemplary embodiment of one half ofthe pod of the cassette system;

FIG. 48A is a pictorial view of the exemplary embodiment of the podmembrane of the cassette system;

FIG. 48B is a pictorial view of the exemplary embodiment of the podmembrane of the cassette system;

FIG. 49 is an exploded view of an exemplary embodiment of the pod of thecassette system;

FIG. 50A is an exploded view of one embodiment of a check valve fluidline in the cassette system;

FIG. 50B is an exploded view of one embodiment of a check valve fluidline in the cassette system;

FIG. 50C is an isometric view of an exemplary embodiment of a fluid linein the cassette system;

FIG. 51A is one embodiment of the fluid flow-path schematic of thecassette system integrated;

FIG. 51B is one embodiment of the fluid flow-path schematic of thecassette system integrated;

FIGS. 52A-52F are various views of one embodiment of the block forconnecting the pneumatic tubes to the manifold according to oneembodiment of the present system;

FIG. 53 is a view of another exemplary sensor manifold;

FIG. 54 is a view of the fluid paths within the exemplary sensormanifold shown in FIG. 53 ;

FIG. 55 is a side view of the exemplary sensor manifold shown in FIG. 53;

FIG. 56A is a cross sectional view of the exemplary sensor manifoldshown in FIG. 53 at cross section A-A of FIG. 56B;

FIG. 56B is a front view of the exemplary sensor manifold shown in FIG.53 ;

FIG. 57 is an exploded view of the exemplary sensor manifold shown inFIG. 53 ;

FIG. 58 is a view of a printed circuit board and media edge connector inaccordance with the exemplary sensor manifold shown in FIG. 53 ;

FIG. 59 is an exemplary fluid schematic of a hemodialysis system;

FIG. 60 is a perspective view of an exemplary embodiment of a userinterface/treatment device combination;

FIG. 61 is a schematic view of an exemplary hardware configuration foreach of the dialysis unit and the user interface unit shown in FIG. 60 ;

FIG. 62 is a schematic view showing exemplary software processes thatmay execute on the automation computer and user interface computer shownin FIG. 61 ;

FIG. 63 is a schematic view showing an exemplary flow of informationbetween and among the hardware and software components of the userinterface computer and automation computer;

FIG. 64 is a schematic view of an exemplary hierarchical state machine(HSM) that may be used by the UI Controller shown in FIG. 63 ;

FIG. 65 is a schematic view of normal screen displays and alarm screendisplays that may be displayed by the user interface shown in FIG. 61 ;

FIG. 66 is a schematic view showing how the Therapy Layer interfaceswith other layers, such as the Machine Layer and User Interface ModelLayer;

FIG. 67 is a schematic view showing an exemplary implementation of theMachine Layer shown in FIG. 66 ;

FIG. 68 is a schematic view showing shows an exemplary implementation ofthe Recycle Preparation application;

FIGS. 69 a-b are schematic views showing shows an exemplaryimplementation of the Clean Blood Path application;

FIGS. 70 a-b are schematic views showing shows an exemplaryimplementation of the Disinfect application;

FIG. 71 is a schematic view showing shows an exemplary implementation ofthe Rinse Endotoxins application;

FIG. 72 is a schematic view showing shows an exemplary implementation ofthe Treatment Preparation application;

FIGS. 73 a-d are schematic views showing shows an exemplaryimplementation of the Patient Connect application;

FIGS. 74 a-b are schematic views showing shows an exemplaryimplementation of the Dialyze application;

FIGS. 75 a-e are schematic views showing shows an exemplaryimplementation of the Solution Infusion application;

FIGS. 76 a-b are schematic views showing shows an exemplaryimplementation of the Rinseback application;

FIG. 77 is a schematic view showing shows an exemplary implementation ofthe Take Samples application;

FIG. 78A is a template showing how the partial diagrams of FIGS. 78B and78C should be joined for viewing of the complete Replace Componentsapplication protocol;

FIG. 78B and FIG. 78C are schematic views each showing a portion of anexemplary implementation of the Replace Components application;

FIGS. 79 a-b are schematic views showing shows an exemplaryimplementation of the Install Chemicals application; and

FIG. 80 shows, in the context of the hemodialysis system, a pathwaybetween a pressurized air tank and a dialysate tank.

DETAILED DESCRIPTION

The present invention generally relates to hemodialysis and similarextracorporeal blood treatment systems, including a variety of systemsand methods that would make hemodialysis more efficient, easier, and/ormore affordable. One aspect of the invention is generally directed tonew fluid circuits for fluid flow. In one set of embodiments, ahemodialysis system may include a blood flow path and a dialysate flowpath, where the dialysate flow path includes one or more of a balancingcircuit, a mixing circuit, and/or a directing circuit. Preparation ofdialysate by the mixing circuit, in some instances, may be decoupledfrom patient dialysis. In some cases, the circuits are defined, at leastpartially, within one or more cassettes, optionally interconnected withconduits, pumps, or the like. In one embodiment, the fluid circuitsand/or the various fluid flow paths may be at least partially isolated,spatially and/or thermally, from electrical components of thehemodialysis system. In some cases, a gas supply may be provided influid communication with the dialysate flow path and/or the dialyzerthat, when activated, is able to urge dialysate to pass through thedialyzer and urge blood in the blood flow path back to the patient. Sucha system may be useful, for example, in certain emergency situations(e.g., a power failure) where it is desirable to return as much blood tothe patient as possible. The hemodialysis system may also include, inanother aspect of the invention, one or more fluid handling devices,such as pumps, valves, mixers, or the like, which can be actuated usinga control fluid, such as air. In some cases, the control fluid may bedelivered to the fluid handling devices using an external pump or otherdevice, which may be detachable in certain instances. In one embodiment,one or more of the fluid handling devices may be generally rigid (e.g.,having a spheroid shape), optionally with a diaphragm contained withinthe device, dividing it into first and second compartments.

Various aspects of the present invention are generally directed to newsystems for hemodialysis and the like, such as hemofiltration systems,hemodiafiltration systems, plasmapheresis systems, etc. Accordingly,although the various systems and methods described herein are describedin relation to hemodialysis, it should be understood that the varioussystems and method described herein are applicable to other dialysissystems and/or in any extracorporeal system able to treat blood or otherbodily fluids, such as plasma.

As discussed above, a hemodialysis system typically includes a bloodflow path and a dialysate flow path. It should be noted that within suchflow paths, the flow of fluid is not necessarily linear, and there maybe any number of “branches” within the flow path that a fluid can flowfrom an inlet of the flow path to an outlet of the flow path. Examplesof such branching are discussed in detail below. In the blood flow path,blood is drawn from a patient, and is passed through a dialyzer, beforebeing returned to the patient. The blood is treated by the dialyzer, andwaste molecules (e.g., urea, creatinine, etc.) and water are passed fromthe blood, through a semi-permeable membrane in the dialyzer, into adialysate solution that passes through the dialyzer by the dialysateflow path. In various embodiments, blood may be drawn from the patientfrom two lines (e.g., an arterial line and a venous line, i.e., “dualneedle” flow), or in some cases, blood may be drawn from the patient andreturned through the same needle (e.g., the two lines may both bepresent within the same needle, i.e., “single needle” flow). In stillother embodiments, a “Y” site or “T” site is used, where blood is drawnfrom the patient and returned to the patient through one patientconnection having two branches (one being the fluid path for the drawnblood, the second the fluid path for the return blood). In anembodiment, a “Y” or “T” connection can be made with a single-lumenneedle or catheter. In another embodiment, a “dual needle” flow effectcan be obtained with the use of a single catheter or needle having duallumens. The patient may be any subject in need of hemodialysis orsimilar treatments, although typically the patient is a human. However,hemodialysis may be performed on non-human subjects, such as dogs, cats,monkeys, and the like.

In the dialysate flow path, fresh dialysate is prepared and is passedthrough the dialyzer to treat the blood from the blood flow path. Thedialysate may also be equalized for blood treatment within the dialyzer(i.e., the pressure between the dialysate and the blood are equalized),i.e., the pressure of dialysate through the dialyzer is closely matchedto the pressure of blood through the dialyzer, often exactly, or in someembodiments, at least within about 1% or about 2% of the pressure of theblood. In some cases, it may be desirable to maintain a greater pressuredifference (either positive or negative) between the blood flow path anddialysate flow path. After passing through the dialyzer, the useddialysate, containing waste molecules (as discussed below), is discardedin some fashion. In some cases, the dialysate is heated prior totreatment of the blood within the dialyzer using an appropriate heater,such as an electrical resistive heater. The dialysate may also befiltered to remove contaminants, infectious organisms, debris, and thelike, for instance, using an ultrafilter. The ultrafilter may have amesh or pore size chosen to prevent species such as these from passingtherethrough. For instance, the mesh or pore size may be less than about0.3 micrometers, less than about 0.2 micrometers, less than about 0.1micrometers, or less than about 0.05 micrometers, etc. The dialysate isused to draw waste molecules (e.g., urea, creatinine, ions such aspotassium, phosphate, etc.) and water from the blood into the dialysatethrough osmosis or convective transport, and dialysate solutions arewell-known to those of ordinary skill in the art.

The dialysate typically contains various ions such as sodium chloride,bicarbonate, potassium and calcium that are similar in concentration tothat of normal blood. In some cases, the bicarbonate, may be at aconcentration somewhat higher than found in normal blood. Typically, thedialysate is prepared by mixing water from a water supply with one ormore ingredients: an “acid” (which may contain various species such asacetic acid, dextrose, NaCl, CaCl, KCl, MgCl, etc.), sodium bicarbonate(NaHCO₃), and/or sodium chloride (NaCl). The preparation of dialysate,including using the appropriate concentrations of salts, osmolarity, pH,and the like, is well-known to those of ordinary skill in the art. Asdiscussed in detail below, the dialysate need not be prepared at thesame rate that the dialysate is used to treat the blood. For instance,the dialysate can be made concurrently or prior to dialysis, and storedwithin a dialysate storage vessel or the like.

Within the dialyzer, the dialysate and the blood typically do not comeinto physical contact with each other, and are separated by asemi-permeable membrane. Typically, the semipermeable membrane is formedfrom a polymer such as cellulose, polyarylethersulfone, polyamide,polyvinylpyrrolidone, polycarbonate, polyacrylonitrile, or the like,which allows the transport of ions or small molecules (e.g., urea,water, etc.), but does not allow bulk transport or convection duringtreatment of the blood. In some cases, even larger molecules, such asbeta-2-microglobulin, may pass through the membrane. In other cases,convective transfer of fluid, ions and small molecules can occur, forexample, when there is a hydrostatic pressure difference across thesemi-permeable membrane.

The dialysate and the blood do not come into contact with each other inthe dialyzer, and are usually separated by the membrane. Often, thedialyzer is constructed according to a “shell-and-tube” designcomprising a plurality of individual tubes or fibers (through whichblood flows), formed from the semipermeable membrane, surrounded by alarger “shell” through which the dialysate flows (or vice versa in somecases). Flow of the dialysate and the blood through the dialyzer can becountercurrent, or concurrent in some instances. Dialyzers arewell-known to those of ordinary skill in the art, and are obtainablefrom a number of different commercial sources.

In one aspect, the dialysate flow path can be divided into one or morecircuits, such as a balancing circuit, a mixing circuit, and/or adirecting circuit. It should be noted that a circuit, in reference tofluid flow, is not necessarily fluidically isolated, i.e., fluid mayflow into a fluid circuit and out of a fluid circuit. Similarly, a fluidmay pass from one fluid circuit to another fluid circuit when the fluidcircuits are in fluid communication or are fluidly connected to eachother. It should be noted that, as used herein, “Fluid” means anythinghaving fluidic properties, including but not limited to, gases such asair, and liquids such as water, aqueous solution, blood, dialysate, etc.

A fluid circuit is typically a well-defined module that receives acertain number of fluid inputs and in some cases performs one or moretasks on the fluid inputs, before directing the fluids to appropriateoutputs. In certain embodiments of the invention, as discussed below,the fluid circuit is defined as a cassette. As a specific example, adialysate flow path may include a balancing circuit, a directingcircuit, and a mixing circuit. As another example, a blood flow path mayinclude a blood flow circuit. Within the balancing circuit, dialysate isintroduced into the balancing circuit and pumps operate on the dialysatesuch that the pressure of dialysate passing through the dialyzerbalances the pressure of blood passing through the dialysate, aspreviously discussed. Similarly, within the directing circuit, freshdialysate is passed from the mixing circuit to the balancing circuit,while used dialysate is passed from the balancing circuit to a drain.Within the mixing circuit, ingredients and water are mixed together toform fresh dialysate. The blood flow circuit is used to draw blood fromthe patient, pass the blood through a dialyzer, and return the blood tothe patient. These circuits will be discussed in detail below.

An example of a hemodialysis system having such fluid circuits isillustrated schematically in FIG. 2A as a high-level overview. FIG. 2Aillustrates a dialysis system 5 that includes a blood flow circuit 10,through which blood passes from a patient to a dialyzer 14, and throughwhich treated blood returns to the patient. The hemodialysis system inthis example also includes a balancing circuit 143 (part of an internalor inner dialysate circuit), which takes dialysate after it passesthrough an ultrafilter 73 and passes the dialysate through dialyzer 14,with used dialysate returning to balancing circuit 143 from dialyzer 14.A directing circuit 142 (part of an external or outer dialysate circuit)handles fresh dialysate before it passes through ultrafilter 73. Amixing circuit 25 prepares dialysate, for instance, on an as-neededbasis, during and/or in advance of dialysis, etc., using variousingredients 49 and water. The directing circuit 142 can also receivewater from a water supply 30 and pass it to mixing circuit 25 forpreparation of the dialysate, and the directing circuit 142 can alsoreceive used dialysate from balancing circuit 143 and pass it out ofsystem 5 as waste via drain 31. Also shown, in dotted lines, areconduits 67 that can be connected between blood flow circuit 10, anddirecting circuit 142, e.g., for disinfection of the hemodialysissystem. In one set of embodiments, one or more of these circuits (e.g.,the blood flow circuit, the balancing circuit, the directing circuit,and/or the mixing circuit) may include a cassette incorporating thevalves and pumps needed for controlling flow through that portion.Examples of such systems are discussed in detail below.

FIG. 2B is a schematic representation of a hemodialysis system accordingto one embodiment of the invention. In this schematic, a blood flowcassette 22 is used to control flow through the blood flow circuit 10,and a dialysate cassette 21 is used to control flow through thedialysate circuit. The blood flow cassette includes at least one inletvalve 24 (in other embodiments, more than one inlet valve is included)to control the flow of blood through cassette 22 as well as ananticoagulant valve or pump 12 to control the flow of anticoagulant intothe blood, and a blood flow pump 13, which may include a pair of podpumps in some cases. These pod pumps may be of the type (or variationsof the type) as described in U.S. Provisional Patent Application Ser.No. 60/792,073, filed Apr. 14, 2006, entitled “Extracorporeal ThermalTherapy Systems and Methods”; or in U.S. patent application Ser. No.11/787,212, filed Apr. 13, 2007, entitled “Fluid Pumping Systems,Devices and Methods,” each of which is incorporated herein in itsentirety. All the pumps and valves in this example system may becontrolled by a control system, e.g., an electronic and digital controlsystem, although other control systems are possible in otherembodiments.

Providing two pod pumps may allow for a more continuous flow of bloodthrough the blood flow circuit 10; however, a single pod pump, such as asingle pod pump may be used in other embodiments. The pod pumps mayinclude active inlet and outlet valves (instead of passive check valvesat their inlets and outlets) so that flow in the blood flow circuit 10may be reversed under some conditions. For instance, by reversing flowin the blood flow circuit, the hemodialysis system can check whether theoutlet of the blood flow circuit is properly connected to the patient sothat the treated blood is correctly returned to the patient. If, forexample, the patient connection point has been disconnected, e.g., byfalling out, reversing the blood flow pump would draw air rather thanblood. This air can be detected by standard air detectors incorporatedinto the system.

In another embodiment, blood outlet valve 26 and air trap/filter 19,which are located downstream of the dialyzer, may be incorporated intoblood flow cassette 22. The pod pumps and all the valves (including thevalves associated with the pod pumps' inlets and outlets) in the bloodflow cassette 22 may be actuated pneumatically. Sources of positive andnegative gas pressure in one embodiment, are provided by a base unitholding cassette or other device holding the cassette. However, in otherembodiments, the positive and negative gas pressure may be provided byan external device fluidly connected to the cassettes, or any devicebuild into the system The pump chamber may be actuated in the mannerdescribed in U.S. Provisional Patent Application Ser. No. 60/792,073,filed Apr. 14, 2006, entitled “Extracorporeal Thermal Therapy Systemsand Methods”; or in U.S. patent application Ser. No. 11/787,212, filedApr. 13, 2007, entitled “Fluid Pumping Systems, Devices and Methods,”referred to hereinabove. For instance, the pumps may be controlled andthe end of stroke detected in the manner described below. The blood flowcassette 22 may also contain an integrally formed spike for receiving avial of anticoagulant.

The anticoagulant pump, in one embodiment, includes three fluid valves(which may be controlled with a control fluid) and a single pumpingcompartment (although there may be more than one pumping compartment inother embodiments. The valves may connect the compartment to a filteredair vent, to a vial of anticoagulant (or other anticoagulant supply,such as a bag or a bottle, etc.), or to the blood flow path. Theanticoagulant pump can be operated by sequencing the opening and closingof the fluid valves and controlling the pressure in the pumpcompartment, e.g., via the control fluid. When the anticoagulant isremoved from the vial it may be replaced with an equal volume of air,e.g., to keep pressure within the vial relatively constant. Thisreplacement of anticoagulant volume with air may be accomplished, forexample, by (i) opening the valve from the filtered air vent to the pumpcompartment, (ii) drawing air into the compartment by connecting thenegative pressure source to the chamber, (iii) closing the air ventvalve, (iv) opening the valve connecting the compartment to the vial,and (v) pushing air into the vial by connecting the positive pressuresource to the compartment. The anticoagulant can be pumped from the vialinto the blood flow path with a similar sequence, using the valves tothe vial and the blood path rather than the valves to the air vent andthe vial.

FIG. 3A is a schematic diagram showing a specific embodiment of thegeneral overview shown in FIG. 2A. FIG. 3A shows, in detail, how a bloodflow circuit 141, a balancing circuit 143, a directing circuit 142, anda mixing circuit 25 can be implemented on cassettes and made tointerrelate with each other and to a dialyzer 14, an ultrafilter 73,and/or a heater 72, in accordance with one embodiment of the invention.It should be understood, of course, that FIG. 3A is only one possibleembodiment of the general hemodialysis system of FIG. 2A, and in otherembodiments, other fluid circuits, modules, flow paths, layouts, etc.are possible. Examples of such systems are discussed in more detailbelow, and also can be found in the following, each of which isincorporated herein by reference: U.S. Provisional Patent ApplicationSer. No. 60/903,582, filed Feb. 27, 2007, entitled “Hemodialysis Systemand Methods”; U.S. Provisional Patent Application Ser. No. 60/904,024,filed Feb. 27, 2007, entitled “Hemodialysis System and Methods”; U.S.patent application Ser. No. 11/871,680, filed Oct. 12, 2007, entitled“Pumping Cassette”; U.S. patent application Ser. No. 11/871,712, filedOct. 12, 2007, entitled “Pumping Cassette”; U.S. patent application Ser.No. 11/871,787, filed Oct. 12, 2007, entitled “Pumping Cassette”; U.S.patent application Ser. No. 11/871,793, filed Oct. 12, 2007, entitled“Pumping Cassette”; or U.S. patent application Ser. No. 11/871,803,filed Oct. 12, 2007, entitled “Cassette System Integrated Apparatus.”

The components in FIG. 3A will be discussed in detail below. Briefly,blood flow circuit 141 includes an anticoagulant supply 11 and a bloodflow pump 13 which pumps blood from a patient to a dialyzer 14. Theanticoagulant supply 11, although shown in the path of blood flowingtowards the dialyzer, in other embodiments, may be instead located inthe path of blood flowing towards the patient, or in another suitablelocation, such as upstream or downstream of blood flow pump 13. Theanticoagulant supply 11 may be placed in any location downstream fromblood flow pump 13. Balancing circuit 143 includes two dialysate pumps15, which also pump dialysate into dialyzer 14, and a bypass pump 35.Directing circuit 142 includes a dialysate pump 159, which pumpsdialysate from dialysate tank 169 through heater 72 and/or ultrafilter73 to the balancing circuit. Directing circuit 142 also takes wastefluid from balancing circuit 143 and directs it to a drain 31. In somecases, the blood flow circuit 141 can be connected via conduits 67 todirecting circuit 142, e.g., for disinfection, as discussed below.Dialysate flows into dialysate tank 169 from a dialysate supply. In oneembodiment, as is shown in FIG. 3A, the dialysate is produced in mixingcircuit 25. Water from water supply 30 flows through directing circuit142 into mixing circuit 25. Dialysate ingredients 49 (e.g., bicarbonateand acid) are also added into mixing circuit 25, and a series of mixingpumps 180, 183, 184 are used to produce the dialysate, which is thensent to directing circuit 142.

In this example system, one of the fluid circuits is a blood flowcircuit, e.g., blood flow circuit 141 in FIG. 3A. In the blood flowcircuit, blood from a patient is pumped through a dialyzer and then isreturned to the patient. In some cases, blood flow circuit isimplemented on a cassette, as discussed below, although it need not be.The flow of blood through the blood flow circuit, in some cases, isbalanced with the flow of dialysate flowing through the dialysate flowpath, especially through the dialyzer and the balancing circuit.

One example of a blood flow circuit is shown in FIG. 4A. Generally,blood flows from a patient through arterial line 203 via blood flow pump13 to dialyzer 14 (the direction of flow during normal dialysis isindicated by arrows 205; in some modes of operation, however, the flowmay be in different directions, as discussed below). Optionally, ananticoagulant may be introduced into the blood via anticoagulant pump 80from an anticoagulant supply. As shown in FIG. 4A, the anticoagulant canenter the blood flow path after the blood has passed through blood flowpump 13; however, the anticoagulant may be added in any suitablelocation along the blood flow path in other embodiments. For example, inFIG. 4B, the anticoagulant enters the blood flow path before the bloodhas passed through blood flow pump 13. This may be useful, for example,if a blood pump cassette of the type shown in FIGS. 30C-33D is used, andblood flow is directed to cause blood to enter at the top of thecassette, and exit at the bottom of the cassette. The blood pumpchambers can thus additionally serve to trap air that may be present inthe blood before it is pumped to the dialyzer. In other embodiments,anticoagulant supply 11 may be located anywhere downstream from theblood flow pump. After passing through dialyzer 14 and undergoingdialysis, the blood returns to the patient through venous line 204,optionally passing through air trap and/or a blood sample port 19.

As is shown in FIG. 4A, blood flow cassette 141 also includes one ormore blood flow pumps 13 for moving blood through the blood flowcassette. The pumps may be, for instance, pumps that are actuated by acontrol fluid, such as is discussed below. For instance, in oneembodiment, pump 13 may comprise two (or more) pod pumps, e.g., podpumps 23 in FIG. 4A. Each pod pump, in this particular example, mayinclude a rigid chamber with a flexible diaphragm or membrane dividingeach chamber into a fluid compartment and control compartment. There arefour entry/exit valves on these compartments, two on the fluidcompartment and two on the control compartment. The valves on thecontrol compartment of the chambers may be two-way proportional valves,one connected to a first control fluid source (e.g., a high pressure airsource), and the other connected to a second control fluid source (e.g.,a low pressure air source) or a vacuum sink. The fluid valves on thecompartments can be opened and closed to direct fluid flow when the podpumps are pumping. Non-limiting examples of pod pumps are described inU.S. Provisional Patent Application Ser. No. 60/792,073, filed Apr. 14,2006, entitled “Extracorporeal Thermal Therapy Systems and Methods”; orin U.S. patent application Ser. No. 11/787,212, filed Apr. 13, 2007,entitled “Fluid Pumping Systems, Devices and Methods,” each incorporatedherein by reference. Further details of the pod pumps are discussedbelow. If more than one pod pump is present, the pod pumps may beoperated in any suitable fashion, e.g., synchronously, asynchronously,in-phase, out-of-phase, etc.

For instance, in some embodiments, the two-pump pumps can be cycled outof phase to affect the pumping cycle, e.g., one pump chamber fills whilethe second pump chamber empties. A phase relationship anywhere between0° (the pod pumps act in the same direction, filling and emptying inunison) and 180° (the pod pumps act in opposite directions, in which onepod pump fills as the other empties) can be selected in order to impartany desired pumping cycle.

A phase relationship of 180° may yield continuous flow into and out ofthe pod pump cassette. This is useful, for instance, when continuousflow is desired, e.g., for use with dual needle flow or a “Y” or “T”connection. Setting a phase relationship of 0°, however, may be usefulin some cases for single needle flow, in situations in which a “Y” or“T” connection is made with a single needle or single lumen catheter, orin other cases. In a 0° relationship, the pod pumps will first fill fromthe needle, then deliver blood through the blood flow path and back tothe patient using the same needle. In addition, running at phasesbetween 0° and 180° can be used in some cases, to achieve a push/pullrelationship (hemodiafiltration or continuous back flush) across thedialyzer. FIGS. 8A-8C are graphical representations of examples of suchphase relationships. In these figures, the volume or flow of each podpump, the volumes of each pod pumps, and the total hold up volume ofboth pod pumps is shown as a function of time. These times and flowrates are arbitrarily chosen, and are presented here to illustrate therelationships between the pod pumps at different phasings. For instance,at a 180° phase relationship (FIG. 8B), the total hold up volume remainssubstantially constant.

In some cases, an anticoagulant (e.g., heparin, or any otheranticoagulant known to those of ordinary skill in the art) may be mixedwith the blood within blood flow cassette 141 as is shown in FIG. 14 .For instance, the anticoagulant may be contained within a vial 11 (orother anticoagulant supply, such as a tube or a bag), and blood flowcassette 141 may be able to receive the anticoagulant vial with anintegrally formed spike 201 (which, in one embodiment, is a needle) thatcan pierce the seal of the vial. The spike may be formed from plastic,stainless steel, or another suitable material, and may be a sterilizablematerial in some cases, e.g., the material may be able to withstandsufficiently high temperatures and/or radiation so as to sterilize thematerial. As an example, as is shown in FIG. 4A, spike 201 may beintegrally formed with a blood flow cassette 141, and a vial 11 can beplaced onto the spike, piercing the seal of the vial, such thatanticoagulant can flow into blood flow cassette to be mixed with theblood in the blood flow path, or in some cases, mixed with dialysate asdiscussed below.

A third pump 80, which can act as a metering chamber in some cases, inblood flow cassette 141 can be used to control the flow of anticoagulantinto the blood within the cassette. Third pump 80 may be of the same orof a different design than pump 13. For instance, third pump 80 may be apod pump and/or third pump 80 may be actuated by a control fluid, suchas air. For example, third pump 80 may be a membrane-based meteringpump. For instance, as is shown in FIG. 4A, third pump 80 may include arigid chamber with a flexible diaphragm dividing the chamber into afluid compartment and a control compartment. Valves on the controlcompartment of the chamber may be connected to a first control fluidsource (e.g., a high pressure air source), and the other compartmentconnected to a second control fluid source (e.g., a low pressure airsource) or a vacuum sink. Valves on the fluid compartment of the chambercan be opened and closed in response to the control compartment, thuscontrolling the flow of anticoagulant into the blood. Further details ofsuch a pod pump are discussed below. In one set of embodiments, air mayalso be introduced into the blood flow path through a filter 81, asdiscussed below.

Fluid Management System (“FMS”) measurements may be used to measure thevolume of fluid pumped through a pump chamber during a stroke of themembrane, or to detect air in the pumping chamber. FMS methods aredescribed in U.S. Pat. Nos. 4,808,161; 4,826,482; 4,976,162; 5,088,515;and 5,350,357, which are hereby incorporated herein by reference intheir entireties. In some cases, the volume of liquid delivered by ananticoagulant pump, a dialysate pump, or other membrane-based pump isdetermined using an FMS algorithm in which changes in chamber pressuresare used to calculate a volume measurement at the end of a fill strokeand at the end of a delivery stroke. The difference between the computedvolumes at the end of a fill and delivery stroke is the actual strokevolume. This actual stroke volume can be compared to an expected strokevolume for the particular sized chamber. If the actual and expectedvolumes are significantly different, the stroke has not properlycompleted and an error message can be generated.

If stroke volumes are collected with a scale, the calculation can beworked backwards to determine a calibration value for the referencechamber. FMS systems can vent to atmosphere for the FMS measurement.Alternatively, the system can vent to a high pressure positive sourceand a low pressure negative source for the FMS measurement. Doing soprovides the following advantages, amongst others: (1) if the highpressure source is a pressure reservoir with a controlled pressure,there is an opportunity to do a cross check on the pressure sensors ofthe reservoir and chamber to ensure they are similar when the chamber isbeing vented to the reservoir. This can be used to detect a brokenpressure sensor or a failed valve; (2) by using higher/lower pressuresto vent, there are larger pressure differences for the FMS measurementsso better resolution can be obtained.

Blood flow circuit 141 may also include an air trap 19 incorporated intoblood flow circuit 141 in some cases. Air trap 19 may be used to removeair bubbles that may be present within the blood flow path. In somecases, air trap 19 is able to separate any air that may be present fromthe blood due to gravity. In some cases, air trap 19 may also include aport for sampling blood. Air traps are known to those of ordinary skillin the art.

In accordance with another aspect of the invention, the air trap 19 isplaced in the blood flow path after the blood exits the dialyzer andbefore it is returned to the patient. As shown in FIGS. 4C and 4D, airtrap 19 may have a spherical or spheroid-shape container 6, and have itsinlet port 7 located near the top and offset from the vertical axis ofthe container, and an outlet 9 at a bottom of the container. The curvedshape of the inside wall 4 of the trap can thus direct the blood tocirculate along the inside wall as the blood gravitates to the bottom ofthe container, facilitating the removal of air bubbles from the blood.Air present in the blood exiting the outlet 9 of the dialyzer 14 willenter at the top of the air trap 19 and remain at the top of thecontainer as blood flows out the outlet at the bottom and to the venousblood line 204. By locating the inlet port 7 near the top of trap 19, itis also possible to circulate blood through the trap with minimal or noair present within the container (as a “run-full” air trap). The abilityto avoid an air-blood interface for routine circulation of blood in thetrap can be advantageous. Placing the inlet port 7 at or near the top ofthe container also allows most or all of the air present in the trap tobe removed from the trap by reversing the flow of fluid through theblood tubing (i.e. from the bottom to the top of the trap 19, exitingthrough the inlet port of the trap 19). In an embodiment, a self-sealingport 3, such as a self-sealing stopper with a split septum or membrane,or another arrangement, is located at the top of the trap, allowing thewithdrawal of air from the container (e.g., by syringe). The blood-sidesurface of the self-sealing membrane can be situated nearly flush withthe top of the interior of the trap, in order to facilitate cleaning ofthe self-sealing port during disinfection. The self-sealing port 3 canalso serve as a blood sampling site, and/or to allow the introduction ofliquids, drugs or other compounds into the blood circuit. A sealedrubber-type stopper can be used if access with a needle is contemplated.Using a self-sealing stopper with split septum permits sampling andfluid delivery using a needleless system.

Additional fluid connections 82 may allow blood flow circuit 10 to alsobe connected to the patient, and/or to a fluid source for priming ordisinfecting the system, including blood flow circuit 10. Generally,during disinfection, arterial line 203 and venous line 204 are connecteddirectly to directing circuit 142 via conduits 67, such that adisinfecting fluid (e.g., heated water and in some embodiments, acombination heated water and one or more chemical agent) may be flowedthrough dialyzer 14 and blood flow circuit 141 back to directing circuit142 for recirculation, this disinfection is similar to those shown inU.S. Pat. No. 5,651,898 to Kenley, et al., which is incorporated hereinby reference. This is also discussed in more detail below.

The pressure within arterial line 203, to draw blood from the patient,may be kept to a pressure below atmospheric pressure in some cases. If apod pump is used, the pressure within blood flow pump 13 may beinherently limited to the pressures available from the positive andnegative pressure reservoirs used to operate the pump. In the event thata pressure reservoir or valve fails, the pump chamber pressure willapproach the reservoir pressure. This will increase the fluid pressureto match the reservoir pressure until the diaphragm within the pod pump“bottoms” (i.e., is no longer is able to move, due to contact with asurface), and the fluid pressure will not exceed a safe limit and willequilibrate with a natural body fluid pressure. This failure naturallystops operation of the pod pump without any special intervention.

A specific non-limiting example of a blood flow cassette is shown inFIGS. 30-33 . Referring now to FIGS. 30A and 30B, the outer side of thetop plate 900 of an exemplary embodiment of the cassette is shown. Thetop plate 900 includes one half of the pod pumps 820, 828. This half isthe liquid half where the source fluid will flow through. The two fluidpaths 818, 812 are shown. These fluid paths lead to their respective podpumps 820, 828.

The pod pumps 820, 828 include a raised flow path 908, 910. The raisedflow path 908, 910 allows for the fluid to continue to flow through thepod pumps 820, 828 after the diaphragm (not shown) reaches the end ofstroke. Thus, the raised flow path 908, 910 minimizes the diaphragmcausing air or fluid to be trapped in the pod pump 820, 828 or thediaphragm blocking the inlet or outlet of the pod pump 820, 828, whichwould inhibit continuous flow. The raised flow path 908, 910 is shown inone exemplary embodiment having particular dimensions, and in somecases, the dimensions are equivalent to the fluid flow paths 818, 812.However, in alternate embodiments, the raised flow path 908, 910 isnarrower, or in still other embodiments, the raised flow path 908, 910can be any dimensions as the purpose is to control fluid flow so as toachieve a desired flow rate or behavior of the fluid. In someembodiments, the raised flow path 908, 910 and the fluid flow paths 818,812 have different dimensions. Thus, the dimensions shown and describedhere with respect to the raised flow path, the pod pumps, the valves orany other aspect are mere exemplary and alternate embodiments. Otherembodiments are readily apparent.

In one exemplary embodiment of this cassette, the top plate includes aspike 902 as well as a container perch 904. The spike 902 is hollow inthis example, and is fluidly connected to the flow path. In someembodiments, a needle is attached into the spike. In other embodiments,a needle is connected to the container attachment.

Referring now to FIGS. 30C and 30D, the inside of the top plate 900 isshown. The raised flow paths 908, 910 connects to the inlet flow paths912, 916 and outlet flow paths 914, 918 of the pod pumps 820, 828. Theraised flow paths are described in more detail above.

The metering pump (not shown) includes connection to an air vent 906 aswell as connection to the spike's hollow path 902. In one exemplaryembodiment, the air vent 906 includes an air filter (not shown). The airfilter may be a particle air filter in some cases. In some embodiments,the filter is a somicron hydrophobic air filter. In various embodiments,the size of the filter may vary, in some instances the size will dependon desired outcome. The metering pump works by taking air in through theair vent 906, pumping the air to the container of second fluid (notshown) through the spike's hollow path 902 and then pumping a volume ofsecond fluid out of the container (not shown) through the spike's hollowpath 902 and into the fluid line at point 826. This fluid flow path forthe metering pump is shown with arrows on FIG. 30C.

Referring now to FIGS. 31A and 31B, the liquid side of the midplate 1000is shown. The areas complementary to the fluid paths on the inner topplate are shown. These areas are slightly raised tracks that present asurface finish that is conducive to laser welding, which is the mode ofmanufacture in one embodiment. The fluid inlet 810 and fluid outlet 824are also shown in this view.

Referring next to FIGS. 31C and 31D, the air side of the midplate 1000is shown according to one embodiment. The air side of the valve holes808, 814, 816, 822 correspond to the holes in the fluid side of themidplate (shown in FIG. 31A). As seen in FIGS. 33C and 33D, diaphragms1220 complete valves 808, 814, 816, 822 while diaphragms 1226 completepod pumps 820, 828. The metering pump 830 is completed by diaphragm1224. The valves 808, 814, 816, 822, 832, 834, 836 are actuatedpneumatically, and as the diaphragm is pulled away from the holes,liquid is drawn in, and as the diaphragm is pushed toward the holes,liquid is pushed through. The fluid flow is directed by the opening andclosing of the valves 808, 814, 816, 822, 832, 834, 836.

Referring to FIGS. 31A and 31C, the metering pump includes three holes,1002, 1004, 1006. One hole 1002 pulls air into the metering pump, thesecond hole 1004 pushes air to the spike/source container and also,draws liquid from the source container, and the third hole 1006 pushesthe second fluid from the metering pump 830 to the fluid line to point826.

Valves 832, 834, 836 actuate the second fluid metering pump. Valve 832is the second fluid/spike valve, valve 834 is the air valve and valve836 is the valve that controls the flow of fluid to the fluid line toarea 826.

Referring next to FIGS. 32A and 32B, the inner view of the bottom plate1100 is shown. The inside view of the pod pumps 820, 828, the meteringpump 830 and the valves 808, 814, 816, 822, 832, 834, 836 actuation/airchamber is shown. The pod pumps 820, 828, metering pump 830 and thevalves 808, 814, 816, 822, 832, 834, 836 are actuated by a pneumatic airsource. Referring now to FIGS. 32C and 32D, the outer side of the bottomplate 1100 is shown. The source of air is attached to this side of thecassette. In one embodiment, tubes connect to the features on the valvesand pumps 1102. In some embodiments, the valves are ganged, and morethan one valve is actuated by the same air line.

Referring now to FIGS. 33A and 33B, an assembled cassette 1200 with acontainer (or other source) of a second fluid 1202 is shown, which, inthis embodiment, may be an anticoagulant as described above, attached isshown. The container 1202 contains the source of the second fluid and isattached to a hollow spike (not shown) by a container attachment 1206.The spike may be situated within the container attachment 1206, directedupward to penetrate the top of the container 1202, which is held in aninverted position by the container attachment 1206. The spike is influid communication with a fluid channel similar to the hollow path 902depicted in FIGS. 30C and 30D. The air filter 1204 is shown attached tothe air vent (not shown, shown in FIG. 30A as 906). Although not visiblein FIG. 33A, the container perch (shown in FIG. 30A as 904) is under thecontainer attachment 1206.

In some cases, the metering pump is an FMS pump, associated with areference chamber and capable of being monitored with a pressuretransducer to determine the volume of fluid that it delivers. The FMSalgorithm uses changes in pressures to calculate a volume measurement atthe end of a fill stroke and at the end of a delivery stroke. Thedifference between the computed volumes at the end of a fill anddelivery stroke is the actual stroke volume. This actual stroke volumecan be compared to an expected stroke volume for the particular sizedchamber. If the actual and expected volumes are significantly different,the stroke has not properly completed and an error message can begenerated. FMS systems can vent to atmosphere for the FMS measurement.Alternatively, the system can vent to a high pressure positive sourceand a low pressure negative source for the FMS measurement. In one setof embodiments, the metering pump (e.g., the anticoagulant pump) isprimed. Priming the pump removes air from the metering pump and the flowpath, and ensures that the pressure in the fluid container (e.g., theanticoagulant vial) is acceptable.

The metering pump can be designed such that air in the pump chamberflows up into the vial. The test is performed by closing all of themetering pump fluid valves, measuring the external volume, charging thepump's FMS chamber with vacuum, opening valves to draw from the vialinto the pumping chamber, measuring the external volume (again),charging the FMS chamber with pressure, opening the valves to push fluidback into the vial, and then measuring the external volume (again).Changes in external volume resulting from fluid flow should correspondto the known volume of the pumping chamber. If the pumping chambercannot fill from the vial, then the pressure in the vial is too low andair must be pumped in. Conversely, if the pumping chamber cannot emptyinto the vial, then the pressure in the vial is too high and some of theanticoagulant must be pumped out of the vial. Anticoagulant pumped outof the vial during these tests can be discarded, e.g., through thedrain.

During routine delivery of heparin or other medication to the bloodpath, the pressure in the vial can be measured periodically. If the vialpressure is approaching a predefined threshold value below atmosphericpressure, for example, the metering pump can first introduce air intothe vial via the metering pump air vent, normalizing the pressure in thevial and helping to ensure the withdrawal of a reasonably precise amountof medication from the vial. If the vial pressure approaches apredefined threshold value above atmospheric pressure, the metering pumpcan forego instilling any further air into the vial before the nextwithdrawal of medication from the vial.

An exploded view of the assembled cassette 1200 shown in FIGS. 33A and12B is shown in FIGS. 33C and 33D. In these views, an exemplaryembodiment of the pod pump diaphragms 1226 is shown. The gasket of thediaphragm provides a seal between the liquid chamber (in the top plate900) and the air/actuation chamber (in the bottom plate 1100). Thedimpled texture on the dome of diaphragms 1226 provide, amongst otherfeatures, additional space for air and liquid to escape the chamber atthe end of stroke.

A system of the present invention may also include a balancing circuit,e.g., balancing circuit 143 as shown in FIG. 3A. In some cases, bloodflow circuit is implemented on a cassette, although it need not be.Within the balancing circuit, the flow of dialysate that passes in andout of the dialyzer may be balanced in some cases such that essentiallythe same amount of dialysate comes out of the dialyzer as goes into it(however, this balance can be altered in certain cases, due to the useof a bypass pump, as discussed below).

In addition, in some cases, the flow of dialysate may also be balancedthrough the dialyzer such that the pressure of dialysate within thedialyzer generally equals the pressure of blood through the blood flowcircuit. The flow of blood through the blood flow circuit 141 anddialyzer in some cases is synchronized with the flow of dialysate in thedialysate flow path through the dialyzer. Because of the potential offluid transfer across the semi-permeable membrane of the dialyzer, andbecause the pumps of the balancing circuit run at positive pressures,the balancing circuit pumps can be timed to synchronize delivery strokesto the dialyzer with the delivery strokes of the blood pumps, usingpressure and control data from the blood flow pumps.

A non-limiting example of a balancing circuit is shown in FIG. 5 . Inbalancing circuit 143, dialysate flows from optional ultrafilter 73 intoone or more dialysate pumps 15 (e.g., two as shown in FIG. 5 ). Thedialysate pumps 15 in this figure include two pod pumps 161, 162, twobalancing chambers 341, 342, and pump 35 for bypassing the balancingchambers. The balancing chambers may be constructed such that they areformed from a rigid chamber with a flexible diaphragm dividing thechamber into two separate fluid compartments, so that entry of fluidinto one compartment can be used to force fluid out of the othercompartment and vice versa. Non-limiting examples of pumps that can beused as pod pumps and/or balancing chambers are described in U.S.Provisional Patent Application Ser. No. 60/792,073, filed Apr. 14, 2006,entitled “Extracorporeal Thermal Therapy Systems and Methods”; or inU.S. patent application Ser. No. 11/787,212, filed Apr. 13, 2007,entitled “Fluid Pumping Systems, Devices and Methods,” each incorporatedherein by reference. Additional examples of pod pumps are discussed indetail below. As can be seen in the schematic of FIG. 5 , many of thevalves can be “ganged” or synchronized together in sets, so that all thevalves in a set can be opened or closed at the same time.

More specifically, in one embodiment, balancing of flow works asfollows. FIG. 5 includes a first synchronized, controlled together setof valves 211, 212, 213, 241, 242, where valves 211, 212, 213 are gangedand valves 241 and 242 are ganged, as well as a second synchronized,controlled together set of valves 221, 222, 223, 231, 232, where valves221, 222, 223 are ganged, and valves 231 and 232 are ganged. At a firstpoint of time, the first ganged set of valves 211, 212, 213, 241, 242 isopened while the second ganged set of valves 221, 222, 223, 231, 232 isclosed. Fresh dialysate flows into balancing chamber 341 while useddialysate flows from dialyzer 14 into pod pump 161. Fresh dialysate doesnot flow into balancing chamber 342 since valve 221 is closed. As freshdialysate flows into balancing chamber 341, used dialysate withinbalancing chamber 341 is forced out and exits balancing circuit 143 (theused dialysate cannot enter pod pump 161 since valve 223 is closed).Simultaneously, pod pump 162 forces used dialysate present within thepod pump into balancing chamber 342 (through valve 213, which is open;valves 242 and 222 are closed, ensuring that the used dialysate flowsinto balancing chamber 342). This causes fresh dialysate containedwithin balancing chamber 342 to exit the balancing circuit 143 intodialyzer 14. Also, pod pump 161 draws in used dialysate from dialyzer 14into pod pump 161. This is also illustrated in FIG. 18A.

Once pod pump 161 and balancing chamber 341 have filled with dialysate,the first set of valves 211, 212, 213, 241, 242 is closed and the secondset of valves 221, 222, 223, 231, 232 is opened. Fresh dialysate flowsinto balancing chamber 342 instead of balancing chamber 341, as valve212 is closed while valve 221 is now open. As fresh dialysate flows intobalancing chamber 342, used dialysate within the chamber is forced outand exits balancing circuit, since valve 213 is now closed. Also, podpump 162 now draws used dialysate from the dialyzer into the pod pump,while used dialysate is prevented from flowing into pod pump 161 asvalve 232 is now closed and valve 222 is now open. Pod pump 161 forcesused dialysate contained within the pod pump (from the previous step)into balancing chamber 341, since valves 232 and 211 are closed andvalve 223 is open. This causes fresh dialysate contained withinbalancing chamber 341 to be directed into the dialyzer (since valve 241is now open while valve 212 is now closed). At the end of this step, podpump 162 and balancing chamber 342 have filled with dialysate. This putsthe state of the system back into the configuration at the beginning ofthis description, and the cycle is thus able to repeat, ensuring aconstant flow of dialysate to and from the dialyzer. This is alsoillustrated in FIG. 18B. In an embodiment, the fluid (e.g. pneumatic)pressures on the control side of the balancing chamber valves aremonitored to ensure they are functioning properly.

As a specific example, a vacuum (e.g., 4 p.s.i. of vacuum) can beapplied to the port for the first ganged set of valves, causing thosevalves to open, while positive pressure (e.g., 20 p.s.i. of airpressure, 1 p.s.i. is 6.89475 kilopascals) is applied to the secondganged set of valves, causing those valves to close (or vice versa). Thepod pumps each urge dialysate into one of the volumes in one of thebalancing chambers 341, 342. By forcing dialysate into a volume of abalancing chamber, an equal amount of dialysate is squeezed by thediaphragm out of the other volume in the balancing chamber. In eachbalancing chamber, one volume is occupied by fresh dialysate headingtowards the dialyzer and the other volume is occupied by used dialysateheading from the dialyzer. Thus, the volumes of dialysate entering andleaving the dialyzer are kept substantially equal.

It should be noted that any valve associated with a balancing chambermay be opened and closed under any suitable pressure. However, it may beadvantageous to apply a lower or more controlled pressure to initiateand effect valve closure than the pressure ultimately used to keep thevalve closed (“holding pressure”). Applying the equivalent of theholding pressure to effectuate valve closure may lead to transientpressure elevations in the fluid line sufficient to cause an alreadyclosed downstream valve to leak, adversely affecting the balancing ofdialysate flow into and out of the dialyzer. Causing the dialysate pumpand balancing chamber inlet and/or outlet valves to close under a loweror more controlled pressure may improve the balancing of dialysate flowinto and out of the dialyzer. In an embodiment, this can be achieved,for example, by employing pulse width modulation (“PWM”) to the pressurebeing applied in the fluid control lines of the valves. Without beinglimited to the following theories, the use of moderate or controlledpressure to ‘slow-close’ the valves may be effective for example,because: (1) it is possible that in some cases, the pressure in abalancing chamber can transiently exceed the holding pressure in theclosed balancing chamber outlet valve (caused, for example by applyingexcessive pressure to close the balancing chamber inlet valve againstthe mass of fluid behind the valve diaphragm). The transient elevationof pressure in the fluid line can overcome the holding pressure of theclosed outlet valve, resulting in a leak of fluid and an imbalance offluid delivery between the two sides of the balancing chamber. (2) Also,the presence of air or gas between the balancing chamber and a balancingchamber valve, coupled with a rapid valve closure, could cause excessfluid to be pushed through the balancing chamber without being balancedby fluid from the opposite side of the balancing chamber.

As the diaphragms approach a wall in the balancing chambers (so that onevolume in a balancing chamber approaches a minimum and the other volumeapproaches a maximum), positive pressure is applied to the port for thefirst ganged set of valves, causing those valves to close, while avacuum is applied to the second gangd set of valves, causing thosevalves to open. The pod pumps then each urge dialysate into one of thevolumes in the other of the balancing chambers 341, 342. Again, byforcing dialysate into a volume of a balancing chamber, an equal amountof dialysate is squeezed by the diaphragm out of the other volume in thebalancing chamber. Since, in each balancing chamber, one volume isoccupied by fresh dialysate heading towards the dialyzer and the othervolume is occupied by used dialysate heading from the dialyzer, thevolumes of dialysate entering and leaving the dialyzer are kept equal.

Also shown within FIG. 5 is bypass pump 35, which can direct the flow ofdialysate from dialyzer 14 through balancing circuit 143 without passingthrough either of pod pumps 161 or 162. In this figure, bypass pump 35is a pod pump, similar to those described above, with a rigid chamberand a flexible diaphragm dividing each chamber into a fluid compartmentand a control compartment. This pump may be the same or different fromthe other pod pumps, metering pumps and/or balancing chambers describedabove. For example, this pump may be a pump as was described in U.S.Provisional Patent Application Ser. No. 60/792,073, filed Apr. 14, 2006,entitled “Extracorporeal Thermal Therapy Systems and Methods”; or inU.S. patent application Ser. No. 11/787,212, filed Apr. 13, 2007,entitled “Fluid Pumping Systems, Devices and Methods,” each incorporatedherein by reference. Pod pumps are also discussed in detail below.

When control fluid is used to actuate this pump, dialysate may be drawnthrough the dialyzer in a way that is not balanced with respect to theflow of blood through the dialyzer. The independent action of the bypasspump 35 on the dialysate outlet side of the dialyzer causes anadditional net ultrafiltration of fluid from the blood in the dialyzer.This may cause the net flow of liquid away from the patient, through thedialyzer, towards the drain. Such a bypass may be useful, for example,in reducing the amount of fluid a patient has, which is often increaseddue to the patient's inability to lose fluid (primarily water) throughthe kidneys. As shown in FIG. 5 , bypass pump 35 may be controlled by acontrol fluid (e.g., air), irrespective of the operation of pod pumps161 and 162. This configuration may allow for easier control of netfluid removal from a patient, without the need to operate the balancingpumps (inside and outside dialysate pumps) in a way that would allow forsuch fluid to be withdrawn from the patient. Using this configuration,it is not necessary to operate the inside dialysate pumps either out ofbalance or out of phase with the blood pumps in order to achieve a netwithdrawal of fluid from the patient.

To achieve balanced flow across the dialyzer, the blood flow pump, thepumps of the balancing circuit, and the pumps of the directing circuit(discussed below) may be operated to work together to ensure that flowinto the dialyzer is generally equal to flow out of the dialyzer. Ifultrafiltration is required, the ultrafiltration pump (if one ispresent) may be run independently of some or all of the other bloodand/or dialysate pumps to achieve the desired ultrafiltration rate.

To prevent outgassing of the dialysate, the pumps of the balancingcircuit may be always kept at pressures above atmospheric pressure. Incontrast, however, the blood flow pump and the directing circuit pumpsuse pressures below atmosphere to pull the diaphragm towards the chamberwall for a fill stroke. Because of the potential of fluid transferacross the dialyzer and because the pumps of the balancing circuit runat positive pressures, the balancing circuit pumps may be able to useinformation from the blood flow pump(s) in order to run in a balancedflow mode. The delivery strokes of the balancing circuit chambers to thedialyzer can thus be synchronized with the delivery strokes of the bloodpumps.

In one set of embodiments, when running in such a balanced mode, ifthere is no delivery pressure from the blood flow pump, the balancingcircuit pump diaphragm will push fluid across the dialyzer into theblood and the alternate pod of the balancing circuit will not completelyfill. For this reason, the blood flow pump reports when it is activelydelivering a stroke. When the blood flow pump is delivering a stroke thebalancing pump operates. When the blood flow pump is not deliveringblood, the valves that control the flow from the dialyzer to thebalancing pumps (and other balancing valves ganged together with thesevalves, as previously discussed) may be closed to prevent any fluidtransfer from the blood side to the dialysate side from occurring.During the time the blood flow pump is not delivering, the balancingpumps are effectively frozen, and the stroke continues once the bloodflow pump starts delivering again. The balancing pump fill pressure canbe set to a minimal positive value to ensure that the pump operatesabove atmosphere at minimal impedance. Also, the balancing pump deliverypressure can be set to the blood flow pump pressure to generally matchpressures on either side of the dialyzer, minimizing flow across thedialyzer during delivery strokes of the inside pump.

In some cases, it may be advantageous to have the dialysate pump deliverdialysate to the dialyzer at a pressure higher than the deliverypressure of the blood pump to the dialyzer. This can help to ensure, forexample, that a full chamber of clean dialysate can get delivered to thedialyzer. In an embodiment, the delivery pressure on the dialysate pumpis set sufficiently high to allow the inside pump to finish its stroke,but not so high as to stop the flow of blood in the dialyzer.Conversely, when the dialysate pump is receiving spent dialysate fromthe dialyzer, in some cases it may also be advantageous to have thepressure in the dialysate pump set lower than the outlet pressure on theblood side of the dialyzer. This can help ensure that the receivingdialysate chamber can always fill, in turn ensuring that there is enoughdialysate available to complete a full stroke at the balancing chamber.Flows across the semi-permeable membrane caused by these differentialpressures will tend to cancel each other; and the pumping algorithmotherwise attempts to match the average pressures on the dialysate andblood sides of the dialyzer.

Convective flow that does occur across the dialyzer membrane may bebeneficial, because a constant and repeated shifting of fluid back andforth across the dialyzer in small increments—resulting in no netultrafiltration—can nevertheless help to prevent clot formation withinthe blood tubing and dialyzer, which in turn may allow for a smallerheparin dosage, prolong the useful life of the dialyzer, and facilitatedialyzer cleaning and re-use. Backflushing has the additional benefit ofpromoting better solute removal through convection. In anotherembodiment, a form of continuous backflushing across the dialyzermembrane can also be achieved by making small adjustments to thesynchronization of the delivery strokes of blood with the deliverystrokes of dialysate through the dialyzer.

It is generally beneficial to keep the blood flow as continuous aspossible during therapy, as stagnant blood flow can result in bloodclots. In addition, when the delivery flow rate on the blood flow pumpis discontinuous, the balancing pump must pause its stroke morefrequently, which can result in discontinuous and/or low dialysate flowrates.

However, the flow through the blood flow pump can be discontinuous forvarious reasons. For instance, pressure may be limited within the bloodflow pump, e.g., to +600 mmHg and/or −350 mmHg to provide safe pumpingpressures for the patient. For instance, during dual needle flow, thetwo pod pumps of the blood flow pump can be programmed to run 180° outof phase with one another. If there were no limits on pressure, thisphasing could always be achieved. However to provide safe blood flow forthe patient these pressures are limited. If the impedance is high on thefill stroke (due to a small needle, very viscous blood, poor patientaccess, etc.), the negative pressure limit may be reached and the fillflow rate will be slower then the desired fill flow rate. Thus thedelivery stroke must wait for the previous fill stroke to finishresulting in a pause in the delivery flow rate of the blood flow pump.Similarly, during single needle flow, the blood flow pump may be run at0° phase, where the two blood flow pump pod pumps are simultaneouslyemptied and filled. When both pod pumps are filled, the volumes of thetwo pod pumps are delivered. In an embodiment, the sequence ofactivation causes a first pod pump and then a second pod pump to fill,followed by the first pod pump emptying and then the second pod pumpemptying. Thus the flow in single needle or single lumen arrangement maybe discontinuous.

One method to control the pressure saturation limits would be to limitthe desired flow rate to the slowest of the fill and deliver strokes.Although this would result in slower blood delivery flow rates, the flowrate would still be known and would always be continuous, which wouldresult in more accurate and continuous dialysate flow rates. Anothermethod to make the blood flow rate more continuous in single needleoperation would be to use maximum pressures to fill the pods so the filltime would be minimized. The desired deliver time could then be set tobe the total desired stroke time minus the time that the fill stroketook. However, if blood flow rate cannot be made continuous, thendialysate flow rate may have to be adjusted so that when the blood flowrate is delivering the dialysate flow is higher then the programmedvalue to make up for the time that the dialysate pump is stopped whenthe blood flow pump is filling. The less continuous the blood flow, themore the dialysate flow rate may have to be adjusted upward during blooddelivery to the dialyzer. If this is done with the correct timing, anaverage dialysate flow rate taken over several strokes can still matchthe desired dialysate flow rate.

A non-limiting example of a balancing cassette is shown in FIGS. 34-36 .In one structure of the cassette shown in FIG. 34A, the valves areganged such that they are actuated at the same time. In one embodiment,there are four gangs of valves 832, 834, 836, 838. In some cases, theganged valves are actuated by the same air line. However, in otherembodiments, each valve has its own air line. Ganging the valves asshown in the exemplary embodiment creates the fluid-flow describedabove. In some embodiments, ganging the valves also ensures theappropriate valves are opened and closed to dictate the fluid pathwaysas desired.

In this embodiment, the fluid valves are volcano valves, as described inmore detail herein. Although the fluid flow-path schematic has beendescribed with respect to a particular flow path, in variousembodiments, the flow paths may change based on the actuation of thevalves and the pumps. Additionally, the terms inlet and outlet as wellas first fluid and second fluid are used for description purposes only(for this cassette, and other cassettes described herein as well). Inother embodiments, an inlet can be an outlet, as well as, a first andsecond fluid may be different fluids or the same fluid types orcomposition.

Referring now to FIGS. 35A-35E, the top plate 1000 of an exemplaryembodiment of the cassette is shown. Referring first to FIGS. 35A and35B, the top view of the top plate 1000 is shown. In this exemplaryembodiment, the pod pumps 820, 828 and the balancing pods 812, 822 onthe top plate, are formed in a similar fashion. In this embodiment, thepod pumps 820, 828 and balancing pods 812, 822, when assembled with thebottom plate, have a total volume of capacity of 38 ml. However, invarious embodiments, the total volume capacity can be greater or lessthan in this embodiment. The first fluid inlet 810 and the second fluidoutlet 816 are shown.

Referring now to FIGS. 35C and 35D, the bottom view of the top plate1000 is shown. The fluid paths are shown in this view. These fluid pathscorrespond to the fluid paths shown in FIG. 34B in the midplate 900. Thetop plate 1000 and the top of the midplate form the liquid or fluid sideof the cassette for the pod pumps 820, 828 and for one side of thebalancing pods 812, 822. Thus, most of the liquid flow paths are on thetop and midplates. The other side of the balancing pods' 812, 822 flowpaths are located on the inner side of the bottom plate, not shown here,shown in FIGS. 36A-36B.

Still referring to FIGS. 35C and 35D, the pod pumps 820, 828 andbalancing pods 812, 822 include a groove 1002. The groove 1002 is shownhaving a particular shape, however, in other embodiments, the shape ofthe groove 1002 can be any shape desirable. The shape shown in FIGS. 35Cand 35D is an exemplary embodiment. In some embodiments of the groove1002, the groove forms a path between the fluid inlet side and the fluidoutlet side of the pod pumps 820, 828 and balancing pods 812, 822.

The groove 1002 provides a fluid path whereby when the diaphragm is atthe end of stroke, there is still a fluid path between the inlet andoutlet such that the pockets of fluid or air do not get trapped in thepod pump or balancing pod. The groove 1002 is included in both theliquid and air sides of the pod pumps 820, 828 and balancing pods 812,822 (see FIGS. 36A-36B with respect to the air side of the pod pumps820, 828 and the opposite side of the balancing pods 812, 822).

The liquid side of the pod pumps 820, 828 and balancing pods 812, 822,in one exemplary embodiment, include a feature whereby the inlet andoutlet flow paths are continuous while the outer ring 1004 is alsocontinuous. This feature allows for the seal, formed with the diaphragm(not shown) to be maintained.

Referring to FIG. 35E, the side view of an exemplary embodiment of thetop plate 1000 is shown. The continuous outer ring 1004 of the pod pumps820, 828 and balancing pods 812, 822 can be seen.

Referring now to FIGS. 36A-36E, the bottom plate 1100 is shown.Referring first to FIGS. 36A and 36B, the inside surface of the bottomplate 1100 is shown. The inside surface is the side that contacts thebottom surface of the midplate (not shown, see FIG. 34E). The bottomplate 1100 attaches to the air lines (not shown). The correspondingentrance holes for the air that actuates the pod pumps 820, 928 andvalves (not shown, see FIG. 34E) in the midplate can be seen 1106. Holes1108, 1110 correspond to the second fluid inlet and second fluid outletshown in FIGS. 34C, 824, 826 respectively. The corresponding halves ofthe pod pumps 820, 828 and balancing pods 812, 822 are also shown, asare the grooves 1112 for the fluid paths. Unlike the top plate, thebottom plate corresponding halves of the pod pumps 820, 828 andbalancing pods 812, 822 make apparent the difference between the podpumps 820, 828 and balancing pods 812, 822. The pod pumps 820, 828include an air path on the second half in the bottom plate, while thebalancing pods 812, 822 have identical construction to the half in thetop plate. Again, the balancing pods 812, 822 balance liquid, thus, bothsides of the diaphragm, not shown, will include a liquid fluid path,while the pod pumps 820, 828 are pressure pumps that pump liquid, thus,one side includes a liquid fluid path and the other side, shown in thebottom plate 1100, includes an air actuation chamber or air fluid path.

In one exemplary embodiment of the cassette, sensor elements areincorporated into the cassette so as to discern various properties ofthe fluid being pumped. In one embodiment, the three sensor elements areincluded. In one embodiment, the sensor elements are located in thesensor cell 1114. The cell 1114 accommodates three sensor elements inthe sensor element housings 1116, 1118, 1120. In an embodiment, two ofthe sensor housings 1116, 1118 accommodate a conductivity sensor elementand the third sensor element housing 1120 accommodates a temperaturesensor element. The conductivity sensor elements and temperature sensorelements can be any conductivity or temperature sensor elements in theart. In one embodiment, the conductivity sensor elements are graphiteposts. In other embodiments, the conductivity sensor elements are postsmade from stainless steel, titanium, platinum or any other metal coatedto be corrosion resistant and still be electrically conductive. Theconductivity sensor elements can include an electrical lead thattransmits the probe information to a controller or other device. In oneembodiment, the temperature sensor is a thermistor potted in a stainlesssteel probe. In alternate embodiments, there are either no sensors inthe cassette or only a temperature sensor, only one or more conductivitysensors or one or more of another type of sensor. In some embodiments,the sensor elements are located outside of the cassette, in a separatecassette, and may be connected to the cassette via a fluid line.

Still referring to FIGS. 36A and 36B, the actuation side of the meteringpump 830 is also shown as well as the corresponding air entrance hole1106 for the air that actuates the pump. Referring now to FIGS. 36C and36D, the outer side of the bottom plate 1100 is shown. The valve, podpumps 820, 828 and metering pump 830 air line connection points 1122 areshown. Again, the balancing pods 812, 822 do not have air lineconnection points as they are not actuated by air. As well, thecorresponding openings in the bottom plate 1100 for the second fluidoutlet 824 and second fluid inlet 826 are shown.

Referring now to FIG. 36E, a side view of the bottom plate 1100 isshown. In the side view, the rim 1124 that surrounds the inner bottomplate 1100 can be seen. The rim 1124 is raised and continuous, providingfor a connect point for the diaphragm (not shown). The diaphragm restson this continuous and raised rim 1124 providing for a seal between thehalf of the pod pumps 820, 828 and balancing pods 812, 822 in the bottomplate 1100 and the half of the pod pumps 820, 828 and balancing pods812, 822 in the top plate (not shown, see FIGS. 35A-35D).

As mentioned, dialysate flows from a directing circuit, optionallythrough a heater and/or through an ultrafilter, to the balancingcircuit. In some cases, the directing circuit is implemented on acassette, although it need not be. An example of a directing circuit canbe seen in FIG. 3A as directing circuit 142. Directing circuit 142 isable to perform a number of different functions, in this example. Forinstance, dialysate flows from a dialysate supply (such as from a mixingcircuit, as discussed below) through the directing circuit to abalancing circuit, while used dialysate flows from the balancing circuitto a drain. The dialysate may flow due to the operation of one or morepumps contained within the directing circuit. In some cases, thedirecting circuit may also contain a dialysate tank, which may containdialysate prior to passing the dialysate to the balancing circuit. Sucha dialysate tank, in certain instances, may allow the rate of productionof dialysate to be different than the rate of use of dialysate in thedialyzer within the system. The directing circuit may also direct waterfrom a water supply to the mixing circuit (if one is present). Inaddition, as previously discussed, the blood flow circuit may befluidically connected to the directing circuit for some operations,e.g., disinfection.

Thus, in some cases, dialysate may be made as it is needed, so thatlarge volumes of dialysate do not need to be stored. For instance, afterthe dialysate is prepared, it may be held in a dialysate tank 169. Adialysate valve 17 may control the flow of dialysate from tank 169 intothe dialysate circuit 20. The dialysate may be filtered and/or heatedbefore being sent into the dialyzer 14. A waste valve 18 may be used tocontrol the flow of used dialysate out of the dialysate circuit 20.

One non-limiting example of a directing circuit is shown in FIG. 6 . Inthis figure, directing circuit 142 fluidically connects dialysate from adialysate supply to a dialysate tank 169, then through dialysate pump159, heater 72, and ultrafilter 73, before entering a balancing circuit,as previously discussed. It should be understood that although thisfigure shows that dialysate in the dialysate flow path flows from thedialysate supply to the dialysate tank, the pump, the heater, and theultrafilter (in that order), other orderings are also possible in otherembodiments. Heater 72 may be used to warm the dialysate to bodytemperature, and/or a temperature such that the blood in the blood flowcircuit is heated by the dialysate, and the blood returning to thepatient is at body temperature or higher. Ultrafilter 73 may be used toremove any pathogens, pyrogens, etc. which may be in the dialysatesolution, as discussed below. The dialysate solution then flows into thebalancing circuit to be directed to the dialyzer.

Dialysate tank 169 may comprise any suitable material and be of anysuitable dimension for storing dialysate prior to use. For instance,dialysate tank 169 may comprise plastic, metal, etc. In some cases,dialysate tank may comprise materials similar to those used to form thepod pumps as discussed herein.

The flow of dialysate through directing circuit 142 may be controlled(at least in part) by operation of dialysate pump 159. In addition,dialysate pump 159 may control flow through the balancing circuit. Forinstance, as discussed above with reference to FIG. 5 , fresh dialysatefrom the directing circuit flows into balancing chambers 341 and 342 onbalancing circuit 143; pump 159 may be used as a driving force to causethe fresh dialysate to flow into these balancing chambers. In one set ofembodiments, dialysate pump 159 includes a pod pump, similar to thosedescribed above. The pod pump may include a rigid chamber with aflexible diaphragm dividing each chamber into a fluid compartment andcontrol compartment. The control compartment may be connected to acontrol fluid source, such as an air source. Non-limiting examples ofpumps that may be used as pod pumps and/or balancing chambers aredescribed in U.S. Provisional Patent Application Ser. No. 60/792,073,filed Apr. 14, 2006, entitled “Extracorporeal Thermal Therapy Systemsand Methods”; or in U.S. patent application Ser. No. 11/787,212, filedApr. 13, 2007, entitled “Fluid Pumping Systems, Devices and Methods,”each incorporated herein by reference. Pod pumps are also discussed indetail below.

After passing through pump 159, the dialysate may flow to a heater,e.g., heater 72 in FIG. 6 . The heater may be any heating devicesuitable for heating dialysate, for example, an electrically resistiveheater as is known to those of ordinary skill in the art. The heater maybe kept separated from the directing circuit (e.g., as is shown in FIG.3A), or the heater may be incorporated into the directing circuit, orother circuits as well (e.g., the balancing circuit).

In some cases, the dialysate is heated to a temperature such that bloodpassing through the dialyzer is not significantly chilled. For instance,the temperature of the dialysate may be controlled such that thedialysate is at a temperature at or greater than the temperature of theblood passing through the dialyzer. In such an example, the blood may beheated somewhat, which may be useful in offsetting heat loss caused bythe blood passing through the various components of the blood flowcircuit, as discussed above. In addition, in some cases as discussedbelow, the heater may be connected to a control system such thatdialysate that is incorrectly heated (i.e., the dialysate is too hot ortoo cold) may be recycled (e.g., back to the dialysate tank) or sent todrain instead of being passed to the dialyzer, for example, via line731. The heater may be integrated as part of a fluid circuit, such as adirecting circuit and/or a balancing circuit, or, as is shown in FIG.3A, the heater may be a separate component within the dialysate flowpath.

The heater may also be used, in some embodiments, for disinfection orsterilization purposes. For instance, water may be passed through thehemodialysis system and heated using the heater such that the water isheated to a temperature able to cause disinfection or sterilization tooccur, e.g., temperatures of at least about 70° C., at least about 80°C., at least about 90° C., at least about 100° C., at least about 110°C., etc. In some cases, as discussed below, the water may be recycledaround the various components and/or heat loss within the system may beminimized (e.g., as discussed below) such that the heater is able toheat the water to such disinfection or sterilization temperatures.

The heater may include a control system that is able to control theheater as discussed above (e.g., to bring dialysate up to bodytemperature for dialyzing a patient, to bring the water temperature upto a disinfection temperatures in order to clean the system, etc.).

A non-limiting example of a heater controller follows. The controllermay be selected to be capable of dealing with varying inlet fluidtemperatures as well as for pulsatile or varying flow rates. In additionthe heater control must function properly when flow is directed througheach of the different flow paths (dialyze, disinfect, re-circulate etc).In one embodiment, the heater controller is used on SIP1 boards with anIR (infrared) temperature sensor on the ultra filter and an IRtemperature sensor on the tank. In other embodiments, the board is in abox with less heat losses and to uses conductivity sensors for the inlettemperature sensor. Another embodiment of the controller uses a simpleproportional controller using both tank (heater inlet) and ultrafilter(heater outlet) temperatures, e.g.:

powerHeater=massFlow*((tankPGain*errorTank)+(UFPGain*errorUF),

where:

PowerHeater=heater duty cycle cmd (0-100%);

MassFlow=the fluid mass flow rate;

TankPGain=proportional gain for the tank or inlet temperature sensor;

ErrorTank=difference between the tank or inlet temperature sensor andthe desired temperature;

UFPGain=proportional gain for the ultrafilter or outlet temperaturesensor; and

ErrorUF=difference between the of or outlet temperature sensor and thedesired temperature.

From the heater duty cycle command (0-100%) a PWM command is generated.In some embodiments, this controller may reduce the mass flow rate ifthe given temperature is not maintained and the heater is saturated.

It should be understood that the above-described heater control is byway of example only, and that other heater control systems, and otherheaters, are also possible in other embodiments of the invention.

The dialysate may also be filtered to remove contaminants, infectiousorganisms, pathogens, pyrogens, debris, and the like, for instance,using an ultrafilter. The filter may be positioned in any suitablelocation in the dialysate flow path, for instance, between the directingcircuit and the balancing circuit, e.g., as is shown in FIG. 3A, and/orthe ultrafilter may be incorporated into the directing circuit or thebalancing circuit. If an ultrafilter is used, it may be chosen to have amesh or pore size chosen to prevent species such as these from throughthe filter. For instance, the mesh or pore size may be less than about0.3 micrometers, less than about 0.2 micrometers, less than about 0.1micrometers, or less than about 0.05 micrometers, etc. Those of ordinaryskill in the art will be aware of filters such as ultrafilters, and inmany cases, such filters may be readily obtained commercially.

In some cases, the ultrafilter may be operated such that waste from thefilter (e.g., the retentate stream) is passed to a waste stream, such aswaste line 39 in FIG. 6 . In some cases, the amount of dialysate flowinginto the retentate stream may be controlled. For instance, if theretentate is too cold (i.e., heater 72 is not working, or heater 72 isnot heating the dialysate to a sufficient temperature, the entiredialysate stream (or at least a portion of the dialysate) may bediverted to waste line 39, and optionally, recycled to dialysate tank169 using line 48. Flow from the filter may also be monitored forseveral reasons, e.g., using temperature sensors (e.g., sensors 251 and252), conductivity sensors (for confirming dialysate concentration,e.g., sensor 253), or the like. An example of such sensors is discussedbelow; further non-limiting examples can be seen in U.S. patentapplication Ser. No. 12/038,474 entitled “Sensor Apparatus Systems,Devices and Methods,” filed on Feb. 27, 2008, and incorporated herein byreference.

It should be noted that the ultrafilter and the dialyzer provideredundant screening methods for the removal of contaminants, infectiousorganisms, pathogens, pyrogens, debris, and the like, in this particularexample (although in other cases, the ultrafilter may be absent).Accordingly, for contaminants to reach the patient from the dialysate,the contaminants must pass through both the ultrafilter and thedialyzer. Even in the event that one fails, the other may still be ableto provide sterility and prevent contaminants from reaching thepatient's blood.

Directing circuit 142 may also be able to route used dialysate comingfrom a balancing circuit to a drain, e.g., through waste line 39 todrain 31 in FIG. 6 . The drain may be, for example, a municipal drain ora separate container for containing the waste (e.g., used dialysate) tobe properly disposed of. In some cases, one or more check or “one-way”valves (e.g., check valves 215 and 216) may be used to control flow ofwaste from the directing circuit and from the system. Also, in certaininstances, a blood leak sensor (e.g., sensor 258) may be used todetermine if blood is leaking through the dialyzer into the dialysateflow path. In addition, a liquid sensor can be positioned in acollection pan at the bottom of the hemodialysis unit to indicateleakage of either blood or dialysate, or both, from any of the fluidcircuits.

In addition, directing circuit 142 may receive water from a water supply30, e.g., from a container of water such as a bag, and/or from a deviceable to produce water, e.g., a reverse osmosis device such as those thatare commercially available. In some cases, as is known to those ofordinary skill in the art, the water entering the system is set at acertain purity, e.g., having ion concentrations below certain values.The water entering directing circuit 142 may be passed on to variouslocations, e.g., to a mixing circuit for producing fresh dialysateand/or to waste line 39. In some cases, as discussed below, valves todrain 31, various recycle lines are opened, and conduits 67 may beconnected between directing circuit 142 and blood flow circuit 141, suchthat water is able to flow continuously around the system. If heater 72is also activated, the water passing through the system will becontinuously heated, e.g., to a temperature sufficient to disinfect thesystem. Such disinfection methods will be discussed in detail below.

A non-limiting example of a directing cassette is shown in FIGS. 41-45 .Referring now to FIGS. 41A and 41B, the outer side of the top plate 900of one embodiment of the cassette is shown. The top plate 900 includesone half of the pod pumps 820, 828. This half is the fluid/liquid halfwhere the source fluid will flow through. The inlet and outlet pod pumpfluid paths are shown. These fluid paths lead to their respective podpumps 820, 828.

The pod pumps 820, 828 can include a raised flow path 908, 910. Theraised flow path 908, 910 allows for the fluid to continue to flowthrough the pod pumps 820, 828 after the diaphragm (not shown) reachesthe end of stroke. Thus, the raised flow path 908, 910 minimizes thediaphragm causing air or fluid to be trapped in the pod pump 820, 828 orthe diaphragm blocking the inlet or outlet of the pod pump 820, 828,which would inhibit flow. The raised flow path 908, 910 is shown in thisembodiment having particular dimensions. In alternate embodiments, theraised flow path 908, 910 is larger or narrower, or in still otherembodiments, the raised flow path 908, 910 can be any dimension as thepurpose is to control fluid flow so as to achieve a desired flow rate orbehavior of the fluid. Thus, the dimensions shown and described herewith respect to the raised flow path, the pod pumps, the valves, or anyother aspect are mere exemplary and alternate embodiments. Otherembodiments are readily apparent. FIGS. 41C and 41D show the inner sideof the top plate 900 of this embodiment of the cassette. FIG. 41E showsa side view of the top plate 900.

Referring now to FIGS. 42A and 42B, the fluid/liquid side of themidplate 1000 is shown. The areas complementary to the fluid paths onthe inner top plate shown in FIGS. 41C and 41D are shown. These areasare slightly raised tracks that present a surface finish that isconducive to laser welding, which is one mode of manufacturing in thisembodiment. Other modes of manufacturing the cassette are discussedabove.

Referring next to FIGS. 42C and 42D, the air side, or side facing thebottom plate (not shown, shown in FIGS. 43A-43E) of the midplate 1000 isshown according to this embodiment. The air side of the valve holes 802,808, 814, 816, 822, 836, 838, 840, 842, 844, 856 correspond to the holesin the fluid side of the midplate 1000 (shown in FIGS. 42A and 42B). Asseen in FIGS. 44C and 44D, diaphragms 1220 complete pod pumps 820, 828while diaphragms 1222 complete valves 802, 808, 814, 816, 822, 836, 838,840, 842, 844, 856. The valves 802, 808, 814, 816, 822, 836, 838, 840,842, 844, 856 are actuated pneumatically, and as the diaphragm is pulledaway from the holes, liquid/fluid is allowed to flow. As the diaphragmis pushed toward the holes, fluid flow is inhibited. The fluid flow isdirected by the opening and closing of the valves 802, 808, 814, 816,822, 836, 838, 840, 842, 844, 856. Referring next to FIGS. 43A and 43B,the inner view of the bottom plate 1100 is shown. The inside view of thepod pumps 820, 828, and the valves 802, 808, 814, 816, 822, 836, 838,840, 842, 844, 856 actuation/air chamber is shown. The pod pumps 820,828, and the valves 802, 808, 814, 816, 822, 836, 838, 840, 842, 844,856 are actuated by a pneumatic air source. Referring now to FIGS. 43Cand 43D, the outer side of the bottom plate 1100 is shown. The source ofair is attached to this side of the cassette. In one embodiment, tubesconnect to the tubes on the valves and pumps 1102. In some embodiments,the valves are ganged, and more than one valve is actuated by the sameair line.

Referring now to FIGS. 44A and 44B, an assembled cassette 1200 is shown.An exploded view of the assembled cassette 1200 shown in FIGS. 44A and44B is shown in FIGS. 12C and 12D. In these views, the embodiment of thepod pump diaphragms 1220 is shown. The gasket of the diaphragm providesa seal between the liquid chamber (in the top plate 900) and theair/actuation chamber (in the bottom plate 1100). In some embodiment,texture on the dome of the diaphragms 1220 provide, amongst otherfeatures, additional space for air and liquid to escape the chamber atthe end of stroke. In alternate embodiments of the cassette, thediaphragms may include a double gasket. The double gasket feature wouldbe preferred in embodiments where both sides of the pod pump includeliquid or in applications where sealing both chambers' sides is desired.In these embodiments, a rim complementary to the gasket or other feature(not shown) would be added to the inner bottom plate 1100 for the gasketto seal the pod pump chamber in the bottom plate 1100.

Referring now to FIG. 45 , a cross sectional view of the pod pumps 828in the cassette is shown. The details of the attachment of the diaphragm1220 can be seen in this view. Again, in this embodiment, the diaphragm1220 gasket is pinched by the midplate 1000 and the bottom plate 1100. Arim on the midplate 1000 provides a feature for the gasket to seal thepod pump 828 chamber located in the top plate 900.

Referring next to FIG. 45 , this cross sectional view shows the valves834, 836 in the assembled cassette. The diaphragms 1220 are shownassembled and are held in place, in this embodiment, by being sandwichedbetween the midplate 1000 and the bottom plate 1100. Still referring toFIG. 45 , this cross sectional view also shows a valve 822 in theassembled cassette. The diaphragm 1222 is shown held in place by beingsandwiched between the midplate 1000 and the bottom plate 1100.

In one set of embodiments, dialysate may be prepared separately andbrought to the system for use in the directing circuit. However, in somecases, dialysate may be prepared in a mixing circuit. The mixing circuitmay be run to produce dialysate at any suitable time. For instance,dialysate may be produced during dialysis of a patient, and/or prior todialysis (the dialysate may be stored, for instance, in a dialysatetank. Within the mixing circuit, water (e.g., from a water supply,optionally delivered to the mixing circuit by a directing circuit) maybe mixed with various dialysate ingredients to form the dialysate. Thoseof ordinary skill in the art will know of suitable dialysateingredients, for instance, sodium bicarbonate, sodium chloride, and/oracid, as previously discussed. The dialysate may be constituted on anas-needed basis, so that large quantities do not need to be stored,although some may be stored within a dialysate tank, in certain cases.

FIG. 7A illustrates a non-limiting example of a mixing circuit, whichmay be implemented on a cassette in some cases. In FIG. 7A, water from adirecting circuit flows into mixing circuit 25 due to action of pump180. In some cases, a portion of the water is directed to ingredients49, e.g., for use in transporting the ingredients through the mixingcircuit. As shown in FIG. 7A, water is delivered to bicarbonate source28 (which may also contain sodium chloride in some cases). The sodiumchloride and/or the sodium bicarbonate may be provided, in some cases,in a powdered or granular form, which is moved through the action ofwater. Bicarbonate from bicarbonate source 28 is delivered viabicarbonate pump 183 to a mixing line 186, to which water from thedirecting circuit also flows. Acid from acid source 29 (which may be ina liquid form) is also pumped via acid pump 184 to mixing line 186. Theingredients (water, bicarbonate, acid, NaCl, etc.) are mixed in mixingchamber 189 to produce dialysate, which then flows out of mixing circuit25. Conductivity sensors 178 and 179 are positioned along mixing line186 to ensure that as each ingredient is added to the mixing line, it isadded at proper concentrations.

In one set of embodiments, pump 180 comprises one or more pod pumps,similar to those described above. The pod pumps may include a rigidchamber with a flexible diaphragm dividing each chamber into a fluidcompartment and control compartment. The control compartment may beconnected to a control fluid source, such as an air source. Non-limitingexamples of pumps that can be used as pod pumps are described in U.S.Provisional Patent Application Ser. No. 60/792,073, filed Apr. 14, 2006,entitled “Extracorporeal Thermal Therapy Systems and Methods”; or inU.S. patent application Ser. No. 11/787,212, filed Apr. 13, 2007,entitled “Fluid Pumping Systems, Devices and Methods,” each incorporatedherein by reference. Similarly, in some cases, pumps 183 and/or 184 mayeach be pod pumps. Additional details of pod pumps are discussed below.

In some cases, one or more of the pumps may have pressure sensors tomonitor the pressure in the pump. This pressure sensor may be used toensure that a pump compartment is filling and delivering completely. Forexample, ensuring that the pump delivers a full stroke of fluid may beaccomplished by (i) filling the compartment, (ii) closing both fluidvalves, (iii) applying pressure to the compartment by opening the valvebetween the positive pneumatic reservoir and the compartment, (iv)closing this positive pressure valve, leaving pressurized air in thepath between the valve and the compartment, (v) opening the fluid valveso the fluid can leave the pump compartment, and (vi) monitoring thepressure drop in the compartment as the fluid leaves. The pressure dropcorresponding to a full stroke may be consistent, and may depend on theinitial pressure, the hold-up volume between the valve and thecompartment, and/or the stroke volume. However, in other embodiments ofany of the pod pumps described herein, a reference volume compartmentmay be used, where the volume is determined through pressure and volumedata.

The volumes delivered by the water pump and/or the other pumps may bedirectly related to the conductivity measurements, so the volumetricmeasurements may be used as a cross-check on the composition of thedialysate that is produced. This may ensure that the dialysatecomposition remains safe even if a conductivity measurement becomesinaccurate during a therapy.

FIG. 7B is a schematic diagram showing another example of a mixingcircuit, implementable on a cassette in certain cases. Mixing circuit 25in this figure includes a pod pump 181 for pumping water from a supplyalong a line 186 into which the various ingredients for making thedialysate are introduced into the water. Another pump 182 pumps waterfrom a water supply into source 28 holding the sodium bicarbonate (e.g.,a container) and/or into source 188 holding the sodium chloride. A thirdpump 183 introduces the dissolved bicarbonate into mixing line 186(mixed in mixing chamber 189), while a fourth pump 185 introducesdissolved sodium chloride into line 186 (mixed in mixing chamber 191). Afifth pump 184 introduces acid into the water before it passes throughthe first pump 181. Mixing is monitored using conductivity sensors 178,179, and 177, which each measure the conductivity after a specificingredient has been added to mixing line 186, to ensure that the properamount and/or concentration of the ingredient has been added. An exampleof such sensors is discussed below; further non-limiting examples can beseen in U.S. patent application Ser. No. 12/038,474 entitled “SensorApparatus Systems, Devices and Methods,” filed on Feb. 27, 2008, andincorporated herein by reference.

Referring now to FIG. 3B, in this embodiment, mixing circuit 25constitutes dialysate using two sources: an acid concentrate source 27and a combined sodium bicarbonate (NaHCO₃) and sodium chloride (NaCl)source. As shown in the embodiment shown in FIG. 3B, in someembodiments, the dialysate constituting system 25 may include multiplesof each source. In embodiments of the method where the system is runcontinuously, the redundant dialysate sources allow for continuousfunction of the system, as one set of sources is depleted, the systemuses the redundant source and the first set of sources is replaced. Thisprocess is repeated as necessary, e.g., until the system is shut down.

A non-limiting example of a balancing cassette is shown in FIGS. 34-36 .In the exemplary fluid flow-path cassette shown in FIGS. 37 , valves areopen individually. In this exemplary embodiment, the valves arepneumatically open. Also, in this embodiment, the fluid valves arevolcano valves, as described in more detail elsewhere in thisspecification.

Referring now to FIGS. 38A-38B, the top plate 1100 of one exemplaryembodiment of the cassette is shown. In this exemplary embodiment, thepod pumps 820, 828 and the mixing chambers 818 on the top plate 1100,are formed in a similar fashion. In this exemplary embodiment, the podpumps 820, 828 and mixing chamber 818, when assembled with the bottomplate, have a total volume of capacity of 38 ml. However, in otherembodiments, the mixing chamber may have any size volume desired.

Referring now to FIGS. 38B, the bottom view of the top plate 1100 isshown. The fluid paths are shown in this view. These fluid pathscorrespond to the fluid paths shown in FIGS. 39A-39B in the midplate1200. The top plate 1100 and the top of the midplate 1200 form theliquid or fluid side of the cassette for the pod pumps 820, 828 and forone side of the mixing chamber 818. Thus, most of the liquid flow pathsare on the top 1100 and midplates 1200. Referring to FIG. 39B, the firstfluid inlet 810 and the first fluid outlet 824 are shown.

Still referring to FIGS. 38A and 38B, the pod pumps 820, 828 include agroove 1002 (in alternate embodiments, this is a groove). The groove1002 is shown having a particular size and shape, however, in otherembodiments, the size and shape of the groove 1002 may be any size orshape desirable. The size and shape shown in FIGS. 38A and 38B is oneexemplary embodiment. In all embodiments of the groove 1002, the groove1002 forms a path between the fluid inlet side and the fluid outlet sideof the pod pumps 820, 828. In alternate embodiments, the groove 1002 isa groove in the inner pumping chamber wall of the pod pump.

The groove 1002 provides a fluid path whereby when the diaphragm is atthe end-of-stroke there is still a fluid path between the inlet andoutlet such that the pockets of fluid or air do not get trapped in thepod pump. The groove 1002 is included in both the liquid/fluid andair/actuation sides of the pod pumps 820, 828. In some embodiments, thegroove 1002 may also be included in the mixing chamber 818 (see FIGS.40A-40B with respect to the actuation/air side of the pod pumps 820, 828and the opposite side of the mixing chamber 818. In alternateembodiments, the groove 1002 is either not included or on only one sideof the pod pumps 820, 828.

In an alternate embodiment of the cassette, the liquid/fluid side of thepod pumps 820, 828 may include a feature (not shown) whereby the inletand outlet flow paths are continuous and a rigid outer ring (not shown)is molded about the circumference of the pumping chamber is alsocontinuous. This feature allows for the seal, formed with the diaphragm(not shown) to be maintained. Referring to FIG. 38E, the side view of anexemplary embodiment of the top plate 1100 is shown.

Referring now to FIGS. 39A-39B, an exemplary embodiment of the midplate1200 is shown. The midplate 1200 is also shown in FIGS. 37A-37F, wherethese Figs. correspond with FIGS. 39A-39B. Thus, FIGS. 37A-37F indicatethe locations of the various valves and valving paths. The locations ofthe diaphragms (not shown) for the respective pod pumps 820, 828 as wellas the location of the mixing chamber 818 are shown.

Referring now to FIGS. 39A, in one exemplary embodiment of the cassette,sensor elements are incorporated into the cassette so as to discernvarious properties of the fluid being pumped. In one embodiment, threesensor elements are included. However, in this embodiment, six sensorelements (two sets of three) are included. The sensor elements arelocated in the sensor cell 1314, 1316. In this embodiment, a sensor cell1314, 1316 is included as an area on the cassette for sensor(s)elements. In one embodiment, the three sensor elements of the two sensorcells 1314, 1316 are housed in respective sensor elements housings 1308,1310, 1312 and 1318, 1320, 1322. In one embodiment, two of the sensorelements housings 1308, 1312 and 1318, 1320 accommodate conductivitysensor elements and the third sensor elements housing 1310, 1322accommodates a temperature sensor element. The conductivity sensorelements and temperature sensor elements may be any conductivity ortemperature sensor elements in the art. In one embodiment, theconductivity sensors are graphite posts. In other embodiments, theconductivity sensor elements are posts made from stainless steel,titanium, platinum or any other metal coated to be corrosion resistantand still be electrically conductive. The conductivity sensor elementswill include an electrical lead that transmits the probe information toa controller or other device. In one embodiment, the temperature sensoris a thermistor potted in a stainless steel probe. However, in alternateembodiments, a combination temperature and conductivity sensor elementsis used similar to the one described in a U.S. patent applicationentitled “Sensor Apparatus Systems, Devices and Methods,” filed Oct. 12,2007 (U.S. Patent Publication No. US-2008-0240929-A1).

In alternate embodiments, there are either no sensors in the cassette oronly a temperature sensor, only one or more conductivity sensors or oneor more of another type of sensor.

Referring now to FIGS. 39C, the side view of an exemplary embodiment ofthe midplate 1200 is shown. Referring now to FIGS. 40A-40B, the bottomplate 1300 is shown. Referring first to FIGS. 40A, the inner or insidesurface of the bottom plate 1300 is shown. The inner or inside surfaceis the side that contacts the bottom surface of the midplate (notshown). The bottom plate 1300 attaches to the air or actuation lines(not shown). The corresponding entrance holes for the air that actuatesthe pod pumps 820, 828 and valves (not shown, see FIGS. 37A-37F) in themidplate 1300 can be seen. Holes 810, 824 correspond to the first fluidinlet and first fluid outlet shown in FIGS. 39B, 810, 824 respectively.The corresponding halves of the pod pumps 820, 828 and mixing chamber818 are also shown, as are the grooves 1002 for the fluid paths. Theactuation holes in the pumps are also shown. Unlike the top plate, thebottom plate 1300 corresponding halves of the pod pumps 820, 828 andmixing chamber 818 make apparent the difference between the pod pumps820, 828 and mixing chamber 818. The pod pumps 820, 828 include anair/actuation path on the bottom plate 1300, while the mixing chamber818 has identical construction to the half in the top plate. The mixingchamber 818 mixes liquid and therefore, does not include a diaphragm(not shown) nor an air/actuation path. The sensor cell 1314, 1316 withthe three sensor element housings 1308, 1310, 1312 and 1318, 1320, 1322are also shown.

Referring now to FIGS. 40B, the actuation ports 1306 are shown on theoutside or outer bottom plate 1300. An actuation source is connected tothese actuation ports 1306. Again, the mixing chamber 818 does not havean actuation port as it is not actuated by air. Referring to FIG. 40C, aside view of the exemplary embodiment of the bottom plate 1300 is shown.

As described above, in various aspects of the invention, one or morefluid circuits may be implemented on a cassette, such as the blood flowcircuit, the balancing circuit, the directing circuit, and/or the mixingcircuit, etc. Other cassettes may be present, e.g., a sensing cassetteas is disclosed in U.S. patent application Ser. No. 12/038,474 entitled“Sensor Apparatus Systems, Devices and Methods,” filed on Feb. 27, 2008,and incorporated herein by reference. In some embodiments, some or allof these circuits are combined in a single cassette. In alternateembodiments, these circuits are each defined in respective cassettes. Instill other embodiments, two or more of the fluid circuits are includedon one cassette. In some cases, two, three, or more cassettes may beimmobilized relative to each other, optionally with fluidic connectionsbetween the cassettes. For instance, in one embodiment, two cassettesmay be connected via a pump, such as a pod pump as previously described.The pod pump may include a rigid chamber with a flexible diaphragmdividing each chamber into a first side and a second side, and the sidesmay be used for various purposes as noted above.

Non-limiting examples of cassettes that may be used in the presentinvention include those described in U.S. patent application Ser. No.11/871,680, filed Oct. 12, 2007, entitled “Pumping Cassette”; U.S.patent application Ser. No. 11/871,712, filed Oct. 12, 2007, entitled“Pumping Cassette”; U.S. patent application Ser. No. 11/871,787, filedOct. 12, 2007, entitled “Pumping Cassette”; U.S. patent application Ser.No. 11/871,793, filed Oct. 12, 2007, entitled “Pumping Cassette”; U.S.patent application Ser. No. 11/871,803, filed Oct. 12, 2007, entitled“Cassette System Integrated Apparatus”; or in U.S. patent applicationSer. No. 12/038,648 entitled “Cassette System Integrated Apparatus,”filed on Feb. 27, 2008. Each of these is incorporated by referenceherein in their entireties.

A cassette may also include various features, such as pod pumps, fluidlines, valves, or the like. The cassette embodiments shown and describedin this description include exemplary and various alternate embodiments.However, any variety of cassettes is contemplated that include a similarfunctionality. Although the cassette embodiments described herein areimplementations of the fluid schematics as shown in the figures, inother embodiments, the cassette may have varying fluid paths and/orvalve placement and/or pod pump placements and numbers and thus, isstill within the scope of the invention.

In one example embodiment, a cassette may includes a top plate, amidplate and a bottom plate. There are a variety of embodiments for eachplate. In general, the top plate includes pump chambers and fluid lines,the midplate includes complementary fluid lines, metering pumps andvalves and the bottom plate includes actuation chambers (and in someembodiments, the top plate and the bottom plate include complementaryportions of a balancing chamber or a pod pump).

In general, the diaphragms are located between the midplate and thebottom plate, however, with respect to a balancing chamber or a podpump, a portion of a diaphragm is located between the midplate and thetop plate. Some embodiments include where the diaphragm is attached tothe cassette, either overmolded, captured, bonded, press fit, welded inor any other process or method for attachment, however, in the exemplaryembodiments, the diaphragms are separate from the top plate, midplateand bottom plate until the plates are assembled.

The cassettes may be constructed of a variety of materials. Generally,in the various embodiments, the materials used are solid andnon-flexible. In one embodiment, the plates are constructed ofpolysulfone, but in other embodiments, the cassettes are constructed ofany other solid material and in exemplary embodiment, of anythermoplastic or thermoset.

In one exemplary embodiment, the cassettes are formed by placingdiaphragms in their correct locations (e.g., for one or more pod pumps,if such pod pumps are present), assembling the plates in order, andconnecting the plates. In one embodiment, the plates are connected usinga laser welding technique. However, in other embodiments, the plates maybe glued, mechanically fastened, strapped together, ultrasonicallywelded or any other mode of attaching the plates together.

In practice, the cassette may be used to pump any type of fluid from anysource to any location. The types of fluid include nutritive,nonnutritive, inorganic chemicals, organic chemicals, bodily fluids orany other type of fluid. Additionally, fluid in some embodiments includea gas, thus, in some embodiments, the cassette is used to pump a gas.

The cassette serves to pump and direct the fluid from and to the desiredlocations. In some embodiments, outside pumps pump the fluid into thecassette and the cassette pumps the fluid out. However, in someembodiments, the pod pumps serve to pull the fluid into the cassette andpump the fluid out of the cassette.

As discussed above, depending on the valve locations, control of thefluid paths is imparted. Thus, the valves being in different locationsor additional valves are alternate embodiments of this cassette.Additionally, the fluid lines and paths shown in the figures describedabove are mere examples of fluid lines and paths. Other embodiments mayhave more, less and/or different fluid paths. In still otherembodiments, valves are not present in the cassette.

The number of pod pumps (if pod pumps are present within the cassette)described above may also vary depending on the embodiment. For example,although the various embodiments shown and described above include twopod pumps, in other embodiments, the cassette includes one pod pump. Instill other embodiments, the cassette includes more than two pod pumps,or there may be no pod pumps present. The pod pumps may be single pumpsor multiple pod pumps may be present that can work in tandem, e.g., toprovide a more continuous flow, as discussed above. Either or both maybe used in various embodiments of the cassette. However, as noted above,in some cases, there may be pod pumps not present on a cassette, butcontained between two or more cassettes. Non-limiting examples of suchsystems can be seen in U.S. patent application Ser. No. 12/038,648entitled “Cassette System Integrated Apparatus,” filed on Feb. 27, 2008,and incorporated by herein reference.

The various fluid inlets and fluid outlets disclosed herein may be fluidports in some cases. In practice, depending on the valve arrangement andcontrol, a fluid inlet may be a fluid outlet. Thus, the designation ofthe fluid port as a fluid inlet or a fluid outlet is only fordescription purposes. The various embodiments have interchangeable fluidports. The fluid ports are provided to impart particular fluid pathsonto the cassette. These fluid ports are not necessarily all used all ofthe time; instead, the variety of fluid ports provides flexibility ofuse of the cassette in practice.

Another non-limiting example of a cassette is shown with reference toFIG. 46 . Referring now to FIG. 46A, the assembled cassette systemintegrated is shown. The mixing cassette 500, middle cassette 600 andbalancing cassette 700 are linked by fluid lines or conduits. The podsare between the cassettes. Referring now to FIGS. 46B and 46C, thevarious views show the efficiency of the cassette system integrated. Thefluid lines or conduits 1200, 1300, 1400 are shown in FIG. 50A, FIG. 50Band FIG. 50C respectively. The fluid flows between the cassettes throughthese fluid lines or conduits. Referring now to FIGS. 50A and 50B, thesefluid lines or conduits represent larger 1300 and smaller 1200 checkvalve fluid lines. In the exemplary embodiment, the check valves areduck bill valves; however, in other embodiments, any check valve may beused. Referring to FIG. 50C, fluid line or conduit 1400 is a fluid lineor conduit that does not contain a check valve. For purposes of thisdescription, the terms “fluid line” and “conduit” are used with respectto 1200, 1300 and 1400 interchangeably.

Referring now to FIGS. 46B and 46C, and FIG. 51A, the following is adescription of one embodiment of the fluid flow through the variouscassettes. For ease of description, the fluid flow will begin with themixing cassette 500. Referring now to FIG. 46B and FIG. 51A, the fluidside of the mixing cassette 500 is shown. The fluid side includes aplurality of ports 8000, 8002, 8004, 8006, 8008 and 8010-8026 that areeither fluid inlets or fluid outlets. In the various embodiments, thefluid inlets and outlets may include one or more fluid inlets forreverse osmosis (“RO”) water 8004, bicarbonate, an acid, and a dialysate8006. Also, one or more fluid outlets, including a drain, acid 8002 andat least one air vent outlet as the vent for the dialysate tank. In oneembodiment, a tube (not shown) hangs off the outlet and is the vent (toprevent contamination). Additional outlets for water, bicarbonate andwater mixture, dialysate mixture (bicarbonate with acid and water added)are also included.

The dialysate flows out of the mixing cassette 500, to a dialysate tank(not shown, shown as 1502 in FIG. 51A) and then through a conduit to theinner dialysate cassette 700 (pumped by the outer dialysate cassette 600pod pumps 602 and 604 (604 not shown, shown in FIGS. 46D and 46E). Thefluid paths within the cassettes may vary. Thus, the location of thevarious inlet and outlets may vary with various cassette fluid paths.

Referring now to FIG. 51B, in one embodiment of the cassette system, thecondo cells, conductivity and temperature sensors, are included in aseparate cassette 1504 outside of the cassette system shown in FIGS.46A-46 C. This outside sensor cassette 1504 may be one of thosedescribed in U.S. patent application Ser. No. 12/038,474 entitled“Sensor Apparatus Systems, Devices and Methods,” filed on Feb. 27, 2008,and incorporated herein by reference.

The fluid flow-path for this embodiment is shown in FIG. 51B. In thisembodiment, during the mixing process for the dialysate, the bicarbonatemixture leaves the mixing cassette 500 and flows to an outside sensorcassette, and then flows back into the mixing cassette 500. If thebicarbonate mixture meets pre-established thresholds, acid is then addedto the bicarbonate mixture. Next, once the bicarbonate and acid aremixed in the mixing chamber 506, the dialysate flows out of the cassetteinto the sensor cassette and then back to the mixing cassette 500.

Referring now to FIG. 46D, the mixing cassette 500 include a pneumaticactuation side. In the block shown as 500, there are a plurality ofvalves and two pumping chambers 8030, 8032 build into the cassette 500for pumping or metering the acid or bicarbonate. In some embodiments,additional metering pumps, or less metering pumps, are included. Themetering pumps 8030, 8032 can be any size desired. In some embodiments,the pumps are different sizes with respect to one another, however, inother embodiments, the pumps are the same size with respect to oneanother. For example, in one embodiment, the acid pump is smaller thanthe bicarbonate pump. This may be more efficient and effective whenusing a higher concentration acid, as it may be desirable to use asmaller pump for accuracy and also, it may be desirable for controlschemes to have a smaller pump so as to use full strokes in the controlrather than partial strokes.

The conduits 1200, 1300 include a check-valve. These conduits 1200,1300allow for one-way flow. In the exemplary embodiment, these conduits1200, 1300 all lead to drain. Referring to the flow-path schematic FIG.51A, the locations of these check-valve conduits are apparent. In theembodiment shown, any fluid that is meant for drain flows through themixing cassette 500. Referring again to FIG. 46B, a fluid drain port8006 is located on the fluid side of the cassette 500.

Once the dialysate is mixed, and after the dialysate flows to the sensorcassette (1504 in FIG. 51B) and it is determined that the dialysate isnot within set parameters/thresholds, then the dialysate will be pumpedback into the mixing cassette 500, through a plain conduit 1400 then tothe outer dialysate cassette 600, then back through conduit a checkvalve conduit 1200 and then through the mixing cassette 500 to the drainfluid outlet.

Referring now to FIGS. 46D and 46E, the various pods 502, 504, 506, 602,604, 702, 704, 706, 708 are shown. Each of the pod housings areconstructed identically, however, the inside of the pod housing isdifferent depending on whether the pod is a pod pump 502, 504 602, 604,702, 704 a balancing chamber pods 706, 708 or a mixing chamber pod 504.

Referring now to FIGS. 46D and 46E, together with FIGS. 51A and 51B, thevarious pods are shown both in the fluid flow-path and on the cassettesystem. Pod 502 is the water pod pump and 504 is the bicarbonate waterpod pump (sends water to the bicarbonate) of the mixing cassette 500.Pod 506 is the mixing chamber. Once the dialysate is mixed in the mixingchamber 506, and then flows from the mixing cassette 500 to the sensorcassette 1504, and it is determined that the dialysate qualifies asacceptable, then the dialysate flows to the dialysate tank 1502 throughthe mixing cassette dialysate tank outlet. However, if the dialysate isrendered unacceptable, then the fluid is pumped back into the cassette500, then through a 1400 conduit, to the outer dialysate cassette 600and then pumped through a 1200 check valve conduit, through the mixingcassette 500 and out the drain outlet.

Referring to FIGS. 46A-46C, together with FIGS. 51A-B, the outerdialysate cassette is shown 600 between the mixing cassette 500 and theinner dialysate cassette 700. Pod pumps 602, 604, pump the dialysatefrom the dialysate tank 1502 and send it to the balancing chambers706,708 in the inner dialysate cassette 700 (driving force for thedialysate solution). The outer dialysate cassette 600 pushes thedialysate into the inner dialysate cassette (i.e., the pumps in theinner dialysate cassette 700 do not draw the dialysate in). Thus, fromthe outer dialysate cassette 600, the dialysate is pumped from thedialysate tank 1502, through a heater 1506 and through an ultrafilter1508, and then into the inner dialysate cassette 700.

Still referring now to FIGS. 46D and 46E, together with FIGS. 51A-B, theinner dialysate cassette 700 includes a metering pod 8038 (i.e., anultra filtration metering pod) and includes balancing pods 706, 708 andpod pumps 702, 704. The inner dialysate cassette 700 also includes fluidoutlets and inlets. These inlets and outlets include the outlet to thedialyzer 1510, the inlet from the dialyzer 1510, and a dialysate inlet(the ultrafilter 1508 connects to a port of the inner dialysatecassette). Fluid inlets and outlets are also included for the DCA andDCV connections during priming and disinfection. Various conduits(1200,1300,1400) serve as fluid connections between the cassettes 500,600, 700 and are used for dialysate fluid flow as well as fluid to passthrough in order to drain through the mixing cassette 500. The largestcheck valve 1300 (also shown in FIG. 50B) is the largest check-valve,and is used during disinfection. This tube is larger in order toaccommodate, in the preferred embodiment, blood clots and othercontaminants that flow through the conduits during disinfection.

The valves and pumps of the cassette system are pneumatically actuatedin the exemplary embodiment. The pneumatics attach to the cassettes viaindividual tubes. Thus, each pump, balancing pod, or valve includes anindividual tube connection to a pneumatic actuation manifold (notshown). Referring now to FIGS. 52A-F, the tubes are connected, in theexemplary embodiment, to at least one block, 1600. In some embodiments,more than one block is used to connect the various tubes. The block 1600is dropped into the manifold and then connected to the pneumaticsactuators appropriately. This allows for easy connection of thepneumatic tubes to the manifold.

Referring again to FIG. 46D, the cassette system includes springs 8034,in one embodiment, to aid in holding the system together. The springs8034 hook onto the mixing cassette 500 and inner dialysate cassette 700via catches 8036. However, in other embodiments, any other means orapparatus to assist in maintaining the system in appropriate orientationmay be used including, but not limited to, latching means or elasticmeans, for example.

Referring now to FIGS. 47A-47C, the exemplary embodiment of the pod isshown. The pod includes two fluid ports 902, 904 (an inlet and anoutlet) and the pod may be constructed differently in the variousembodiments. A variety of embodiments of construction are described inU.S. patent application Ser. No. 11/787,212, filed Apr. 13, 2007, andentitled “Fluid Pumping Systems, Devices and Methods,” which is herebyincorporated herein by reference in its entirety.

Referring now to FIGS. 47A, 47D and 47E the groove 906 in the chamber isshown. A groove 906 is included on each half of the pod housing. Inother embodiments, a groove is not included and in some embodiments, agroove is only included on one half of the pod.

Referring now to FIGS. 48A and 48B, the exemplary embodiment of themembrane used in the pod pumps 502, 504 602, 604, 702, 704 is shown.This membrane is shown and described above with respect to FIG. 5A. Inother embodiments, any of the membranes shown in FIGS. 5B-5D may beused. An exploded view of a pod pump according to the exemplaryembodiment is shown FIG. 49 .

Various aspects of the invention include one or more “pod pumps,” usedfor various purposes. The structure of a general pod pump will now bedescribed, although, as noted above, this structure may be modified forvarious uses, e.g., as a pump, a balancing chamber, a mixing chamber, orthe like. In addition, a pod pump may be positioned anywhere in thesystem, for instance, on a cassette or between two or more cassettes,etc.

Generally, a pod pump includes a rigid chamber (which may have anysuitable shape, e.g., spherical, ellipsoid, etc.), and the pod pump mayinclude a flexible diaphragm dividing each chamber into a first half anda second half. In some cases, the rigid chamber is a spheroid. As usedherein, “spheroid” means any three-dimensional shape that generallycorresponds to a oval rotated about one of its principal axes, major orminor, and includes three-dimensional egg shapes, oblate and prolatespheroids, spheres, and substantially equivalent shapes.

Each half of the pod pump may have at least one entry valve, and often(but not always) has at least one exit valve (in some cases, the sameport may be used for both entry and exit). The valves may be, forinstance, open/closing valves or two-way proportional valves. Forinstance, valves on one side of a chamber may be two-way proportionalvalves, one connected to a high pressure source, the other connected toa low pressure (or vacuum) sink, while the valves on the other half maybe opened and closed to direct fluid flow.

In some embodiments, the diaphragm has a variable cross-sectionalthickness. Thinner, thicker or variable thickness diaphragms may be usedto accommodate the strength, flexural and other properties of the chosendiaphragm materials. Thinner, thicker or variable diaphragm wallthickness may also be used to manage the diaphragm thereby encouragingit to flex more easily in some areas than in other areas, thereby aidingin the management of pumping action and flow of subject fluid in thepump chamber. In this embodiment, the diaphragm is shown having itsthickest cross-sectional area closest to its center. However in otherembodiments having a diaphragm with a varying cross-sectional, thethickest and thinnest areas may be in any location on the diaphragm.Thus, for example, the thinner cross-section may be located near thecenter and the thicker cross-sections located closer to the perimeter ofthe diaphragm. In one embodiment of the diaphragm, the diaphragm has atangential slope in at least one section, but in other embodiments, thediaphragm is completely smooth or substantially smooth.

The diaphragm may be made of any flexible material having a desireddurability and compatibility with the subject fluid. The diaphragm maybe made from any material that may flex in response to fluid, liquid orgas pressure or vacuum applied to the actuation chamber. The diaphragmmaterial may also be chosen for particular bio-compatibility,temperature compatibility or compatibility with various subject fluidsthat may be pumped by the diaphragm or introduced to the chambers tofacilitate movement of the diaphragm. In the exemplary embodiment, thediaphragm is made from high elongation silicone. However, in otherembodiments, the diaphragm is made from any elastomer or rubber,including, but not limited to, silicone, urethane, nitrile, EPDM or anyother rubber, elastomer or flexible material.

The shape of the diaphragm is dependent on multiple variables. Thesevariables include, but are not limited to: the shape of the chamber; thesize of the chamber; the subject fluid characteristics; the volume ofsubject fluid pumped per stroke; and the means or mode of attachment ofthe diaphragm to the housing. The size of the diaphragm is dependent onmultiple variables. These variables include, but are not limited to: theshape of the chamber; the size of the chamber; the subject fluidcharacteristics; the volume of subject fluid pumped per stroke; and themeans or mode of attachment of the diaphragm to the housing. Thus,depending on these or other variables, the shape and size of thediaphragm may vary in various embodiments.

The diaphragm may have any thickness. However, in some embodiments, therange of thickness is between 0.002 inches to 0.125 inches (1 inch=2.54cm). Depending on the material used for the diaphragm, the desiredthickness may vary. In one embodiment, high elongation silicone is usedin a thickness ranging from 0.015 inches to 0.050 inches. However inother embodiments, the thickness may vary.

In the exemplary embodiment, the diaphragm is pre-formed to include asubstantially dome-shape in at least part of the area of the diaphragm.Again, the dimensions of the dome may vary based on some or more of thevariables described above. However, in other embodiments, the diaphragmmay not include a pre-formed dome shape.

In the exemplary embodiment, the diaphragm dome is formed using liquidinjection molding. However, in other embodiments, the dome may be formedby using compression molding. In alternate embodiments, the diaphragm issubstantially flat. In other embodiments, the dome size, width or heightmay vary.

In various embodiments, the diaphragm may be held in place by variousmeans and methods. In one embodiment, the diaphragm is clamped betweenthe portions of the cassette, and in some of these embodiments, the rimof the cassette may include features to grab the diaphragm. In others ofthis embodiment, the diaphragm is clamped to the cassette using at leastone bolt or another device. In another embodiment, the diaphragm isover-molded with a piece of plastic and then the plastic is welded orotherwise attached to the cassette. In another embodiment, the diaphragmis pinched between a mid plate and a bottom plate. Although someembodiments for attachment of the diaphragm to the cassette aredescribed, any method or means for attaching the diaphragm to thecassette may be used. The diaphragm, in one alternate embodiment, isattached directly to one portion of the cassette. In some embodiments,the diaphragm is thicker at the edge, where the diaphragm is pinched bythe plates, than in other areas of the diaphragm. In some embodiments,this thicker area is a gasket, in some embodiments an O-ring, ring orany other shaped gasket.

In some embodiments of the gasket, the gasket is contiguous with thediaphragm. However, in other embodiments, the gasket is a separate partof the diaphragm. In some embodiments, the gasket is made from the samematerial as the diaphragm. However, in other embodiments, the gasket ismade of a material different from the diaphragm. In some embodiments,the gasket is formed by over-molding a ring around the diaphragm. Thegasket may be any shape ring or seal desired so as to complement the podpump housing embodiment. In some embodiments, the gasket is acompression type gasket.

Due to the rigid chamber, the pod pump has a generally constant volume.However, within the pod pump, the first and second compartments may havediffering volumes depending on the position of the flexible diaphragmdividing the chamber. Forcing fluid into one compartment may thus causethe fluid within the other compartment of the chamber to be expelled.However, the fluids are typically not able to come into direct contactwith each other within the pod pump due to the presence of the flexiblediaphragm.

Accordingly, in one embodiment, a pod pump used for pumping isconstructed to receive a control fluid in a first compartment and afluid to be pumped in a second compartment. The control fluid may be anyfluid, and may be a liquid or a gas. In one embodiment, the controlfluid is air. Drawing control fluid away from the pod pump (e.g.,through a vacuum, or at least a pressure lower than the pressure withinthe pod pump) causes the pod pump to draw in fluid (e.g., blood,dialysate, etc.) into the other compartment of the pod pump. Similarly,forcing control fluid into the pod pump (e.g., from a high pressuresource) causes the pod pump to expel fluid. By also controlling thevalves of the second compartment, fluid may be brought in through afirst valve and then expelled through a second valve due to action ofthe control fluid.

As another example, a pod pump may be used for fluid balancing, e.g., ofdialysate as discussed above. In such cases, instead of a control fluid,a fluid may be directed to each compartment of the pod pump. Asmentioned, the volume of the pod pump remains generally constant due tothe rigid chamber. Accordingly, when a first volume of fluid is drawninto a first compartment of a balancing pod, an equal volume of fluid isexpelled from the second compartment of the balancing pod (assuming thefluids to be generally incompressible under conditions in which the podis operated). Thus, using such balancing pods, equal volumes of fluidcan be moved. For instance, in FIG. 5 , a balancing pod may allow freshdialysate to enter a first compartment and used dialysate to enter asecond compartment; the volumetric flows of fresh dialysate and useddialysate can be balanced against each other.

In some cases, a pod pump is used that does not contain a flexiblediaphragm dividing the chamber. In such instances, the pod pump can beused as a mixing chamber. For instance, mixing chamber 189 in FIG. 7Amay be such a pod pump.

A non-limiting example of a pod pump is shown in FIG. 9 . This figure isa sectional view of a pneumatically controlled valve that may be used inembodiments of the cassettes. “Pneumatic,” as used herein, means usingair or other gas to move a flexible diaphragm or other member. (Itshould be noted that air is used by way of example only, and in otherembodiments, other control fluids, such as nitrogen (N₂), CO₂, water, anoil, etc. may be used). Three rigid pieces are used, a “top” plate 91, amiddle plate 92, and a “bottom” plate. (The terms “top” and “bottom”only refer to the orientation shown in FIG. 9 . The valve may beoriented in any direction in actual use.) The top and bottom plates 91,93 may be flat on both sides, while the middle plate 92 is provided withchannels, indentations and holes to define the various fluid paths,chamber and ports. A diaphragm 90, along with the middle plate 92,defines a valving chamber 97. Pneumatic pressure is provided through apneumatic port 96 to either force, with positive gas pressure, thediaphragm 90 against a valve seat 99 to close the valve, or to draw,with negative gas pressure, the diaphragm away from the valve seat toopen the valve. A control gas chamber 98 is defined by the diaphragm 90,the top plate 91, and the middle plate 92. The middle plate 92 has anindentation formed on it, into which the diaphragm 90 is placed so as toform the control gas chamber 98 on one side of the diaphragm and thevalving chamber 97 on the other side.

The pneumatic port 96 is defined by a channel formed on the “top”surface of the middle plate 92, along with the top plate 91. Byproviding fluid communication between several valving chambers in acassette, valves may be ganged together so that all the valves gangedtogether may be opened or closed at the same time by a single source ofpneumatic pressure. Channels formed on the “bottom” surface of themiddle plate 92, along with the bottom plate, define the valve inlet 94and the valve outlet 95. Holes formed through the middle plate 92provide communication between the inlet 94 and the valving chamber 97(through the valve seat 99) and between the valving chamber and theoutlet 95.

The diaphragm 90 is provided with a thickened rim 88, which fits tightlyin a groove 89 in the middle plate 92. Thus, the diaphragm 90 may beplaced in and held by the groove 88 before the top plate 91 isultrasonically welded to the middle plate 92, so the diaphragm will notinterfere with the ultrasonic welding of the two plates together, and sothat the diaphragm does not depend on the two plates beingultrasonically welded together in just the right way to be held inplace. Thus, this valve may be manufactured easily without relying onultrasonic welding to be done to very tight tolerances. As shown in FIG.9 , the top plate 91 may include additional material extending intocontrol gas chamber 98 so as to prevent the diaphragm 90 from beingurged too much in a direction away from the groove 89, so as to preventthe diaphragm's thickened rim 88 from popping out of the groove 89.

Pressure sensors may be used to monitor pressure in the pods. Forinstance by alternating applied air pressure to the pneumatic side ofthe chamber, the diaphragm is cycled back and forth across the totalchamber volume. With each cycle, fluid is drawn through the upstreamvalve of the inlet fluid port when the pneumatics pull a vacuum on thepods. The fluid is then subsequently expelled through the outlet portand the downstream valve when the pneumatics deliver positive pressureto the pods.

FIG. 10 is a sectional view of one embodiment of a pod pump that may beincorporated into embodiments of the fluid-control cassettes. In someembodiments, the cassette would incorporate several pod pumps andseveral valves made in accordance with the construction techniques shownin FIGS. 9 and 10 . In such embodiments, the pod pump of FIG. 10 is madefrom different portions of the same three rigid pieces used to make thevalve of FIG. 9 . These rigid pieces are the “top” plate 91, the middleplate 92, and the “bottom” plate. (As noted above, the terms “top” and“bottom” only refer to the orientation shown in FIG. 9 .) To form thepod pump, the top and bottom plates 91, 93 may include generallyhemispheroid portions that together define a hemispheroid pod pump.

A diaphragm 109 separates the central cavity of the pod pump into achamber (the pumping chamber) that receives the fluid to be pumped andanother chamber (the actuation chamber) for receiving the control gasthat pneumatically actuates the pump. An inlet 94 allows fluid to enterthe pumping chamber, and an outlet allows fluid to exit the pumpingchamber. The inlet 94 and the outlet 95 may be formed between middleplate 92 and the bottom plate 93. Pneumatic pressure is provided througha pneumatic port 106 to either force, with positive gas pressure, thediaphragm 109 against one wall of pod pump's cavity to minimize thepumping chamber's volume (as shown in FIG. 10 ), or to draw, withnegative gas pressure, the diaphragm towards the other wall of the podpump's cavity to maximize the pumping chamber's volume.

In some embodiments of the pod pump, various configurations, includinggrooving on one or more plates exposed to the cavity of the pod pump,are used. Amongst other benefits, grooving can prevent the diaphragmfrom blocking the inlet or outlet (or both) flow path for fluid or air(or both).

The diaphragm 109 may be provided with a thickened rim 88, which is heldtightly in a groove 89 in the middle plate 92. Thus, like in the valvingchamber of FIG. 9 , the diaphragm 109 may be placed in and held by thegroove 89 before the top plate 91 is ultrasonically welded to the middleplate 92, so the diaphragm will not interfere with the ultrasonicwelding of the two plates together, and so that the diaphragm does notdepend on the two plates being ultrasonically welded together in justthe right way to be held in place. Thus, this pod pump can bemanufactured easily without relying on ultrasonic welding to be done tovery tight tolerances.

FIG. 11A is a schematic view showing an embodiment of a pressureactuation system 110 for a pod pump, such as that shown in FIG. 10 . Inthis example, air is used as a control fluid (e.g., such that the pumpis pneumatically driven). As mentioned, other fluids (e.g., water) mayalso be used as control fluids in other embodiments.

In FIG. 11A, pressure actuation system 110 alternately provides positiveand negative pressurizations to the gas in the actuation chamber 112 ofthe pod pump 101. The pneumatic actuation system 110 includes anactuation-chamber pressure transducer 114, a variable positive-supplyvalve 117, a variable negative-supply valve 118, a positive-pressure gasreservoir 121, a negative-pressure gas reservoir 122, apositive-pressure-reservoir pressure transducer 115, anegative-pressure-reservoir pressure transducer 116, as well as anelectronic controller 119.

The positive-pressure reservoir 121 provides to the actuation chamber112 the positive pressurization of a control gas to urge the diaphragm109 towards a position where the pumping chamber 111 is at its minimumvolume (i.e., the position where the diaphragm is against the rigidpumping-chamber wall). The negative-pressure reservoir 122 provides tothe actuation chamber 112 the negative pressurization of the control gasto urge the diaphragm 109 in the opposite direction, towards a positionwhere the pumping chamber 111 is at its maximum volume (i.e., theposition where the diaphragm is against the rigid actuation-chamberwall).

A valving mechanism is used in this example to control fluidcommunication between each of these reservoirs 121, 122 and theactuation chamber 112. In FIG. 11A, a separate valve is used for each ofthe reservoirs; a positive-supply valve 117 controls fluid communicationbetween the positive-pressure reservoir 121 and the actuation chamber112, and a negative-supply valve 118 controls fluid communicationbetween the negative-pressure reservoir 122 and the actuation chamber112. These two valves are controlled by an electronic controller 119.(Alternatively, a single three-way valve may be used in lieu of the twoseparate valves 117, 118.) In some cases, the positive-supply valve 117and the negative-supply valve 118 are variable-restriction valves, asopposed to binary on-off valves. An advantage of using variable valvesis discussed below.

The controller 119 also receives pressure information from the threepressure transducers shown in FIG. 11A: an actuation-chamber pressuretransducer 114, a positive-pressure-reservoir pressure transducer 115,and a negative-pressure-reservoir pressure transducer 116. As theirnames suggest, these transducers respectively measure the pressure inthe actuation chamber 112, the positive-pressure reservoir 121, and thenegative-pressure reservoir 122. The controller 119 monitors thepressure in the two reservoirs 121, 122 to ensure they are properlypressurized (either positively or negatively). A compressor-type pump orpumps may be used to attain the desired pressures in these reservoirs121, 122.

In one embodiment, the pressure provided by the positive-pressurereservoir 121 is strong enough, under normal conditions, to urge thediaphragm 109 all the way against the rigid pumping-chamber wall.Similarly, the negative pressure (i.e., the vacuum) provided by thenegative-pressure reservoir 122 is preferably strong enough, undernormal conditions, to urge the diaphragm all the way against the rigidactuation-chamber wall. In some embodiments, however, these positive andnegative pressures provided by the reservoirs 121, 122 are within safeenough limits that even with either the positive-supply valve 117 or thenegative-supply valve 118 open all the way the positive or negativepressure applied against the diaphragm 109 is not so strong as to harmthe patient.

In one embodiment, the controller 119 monitors the pressure informationfrom the actuation-chamber-pressure transducer 114 and, based on thisinformation, controls the valving mechanism (valves 117, 118) to urgethe diaphragm 109 all the way to its minimum-pumping-chamber-volumeposition and then after this position is reached to pull the diaphragm109 all the way back to its maximum-pumping-chamber-volume position.

The pressure actuation system (including the actuation-chamber pressuretransducer 114, the positive-pressure-reservoir pressure transducer 115,the negative-pressure-reservoir pressure transducer 116, the variablepositive-supply valve 117, the variable negative-supply valve 118, thecontroller 119, the positive-pressure gas reservoir 121, and thenegative-pressure gas reservoir 122) is located entirely or mostlyoutside the insulated volume (item 61 of FIG. 6 ). The components thatcome into contact with blood or dialysate (namely, pod pump 101, theinlet valve 105 and the outlet valve 107) may be located, in some cases,in the insulated volume so that they can be more easily disinfected.

Another example of a pressure actuation system 110 for a pod pump isillustrated in FIG. 11B. In this example, pod pump 101 includes apumping chamber 111, an actuation chamber 112, and a diaphragm 109separating the two sides. Fluid ports 102 and 104 allow access of fluidin and out of pumping chamber 111, e.g., through the use of fluid valves(not shown). Within pod pump 101, however, fluid ports 102 and 104include a “volcano” port 126, generally having a raised shape, such thatwhen diaphragm 109 contacts the port, the diaphragm is able to form atight seal against the port. Also shown in FIG. 11B is a 3-way valveconnecting pressure reservoirs 121, 122. The 3-way valve 123 is in fluidcommunication with actuation chamber 112 by a single port in thisexample.

It will be appreciated that other types of actuation systems may be usedto move the diaphragm back and forth instead of the two-reservoirpneumatic actuation system shown in FIGS. 11A-11B.

As noted above, the positive-supply valve 117 and the negative-supplyvalve 118 in the pneumatic actuation system 110 of FIG. 11A arepreferably variable-restriction valves, as opposed to binary on-offvalves. By using variable valves, the pressure applied to the actuationchamber 112 and the diaphragm 109 can be more easily controlled to bejust a fraction of the pressure in reservoir 121, 122, instead ofapplying the full reservoir pressure to the diaphragm. Thus, the samereservoir or set of reservoirs may be used for different pod pumps, eventhough the pressures for operating the pod pumps may differ from podpump to pod pump. Of course, the reservoir pressure needs to be greaterthan the desired pressures to be applied to various pod pump'sdiaphragms, but one pod pump may be operated at, say, half of thereservoir pressure, and another pod pump may be actuated with the samereservoir but at, say, a quarter of the reservoir pressure. Thus, eventhough different pod pumps in the dialysis system are designed tooperate at different pressures, these pod pumps may all share the samereservoir or set of reservoirs but still be actuated at differentpressures, through the use of variable valves. The pressures used in apod pump may be changed to address conditions that may arise or changeduring a dialysis procedure. For example, if flow through the system'stubing becomes constricted because the tubes get twisted, one or both ofthe positive or negative pressures used in the pod pump may be increasedin order to over compensate for the increased restriction.

FIG. 12 is a graph showing how pressures applied to a pod pump may becontrolled using variable valves. The vertical axis represents pressurewith P_(R+) and P_(R−) representing respectively the pressures in thepositive and negative reservoirs (items 121 and 122 in FIG. 11A), andP_(C+) and P_(C−) representing respectively the positive and negativecontrol pressures acting on the pod pump's diaphragm. As can be seen inFIG. 12 , from time T₀ to about time T₁, a positive pressure is appliedto the actuation chamber (so as to force fluid out of the pumpingchamber). By repeatedly reducing and increasing the flow restrictioncaused by the positive variable valve (item 117 in FIG. 11A), thepressure being applied to the actuation chamber can be held at about thedesired positive control pressure, P_(C+). The pressure varies, in asinusoidal manner, around the desired control pressure. Anactuation-chamber pressure transducer (item 114 in FIG. 11A) incommunication with the actuation chamber measures the pressure in theactuation chamber and passes the pressure-measurement information to thecontroller (item 119 in FIG. 11A), which in turn controls the variablevalve so as to cause the actuation chamber's pressure to vary around thedesired control pressure, P_(C+). If there are no fault conditions, thediaphragm is pushed against a rigid wall of the pumping chamber, therebyending the stroke. The controller determines that the end of stroke hasbeen reached when the pressure measured in the actuation chamber nolonger drops off even though the restriction created by the variablevalve is reduced. In FIG. 12 , the end of the expelling stroke occursaround time T₁. When the end of stroke is sensed, the controller causesthe variable valve to close completely so that the actuation chamber'spressure does not increase much beyond the desired control pressure,P_(C+).

After the positive variable valve is closed, the negative variable valve(item 118 in FIG. 11A) is partially opened to allow the negativepressure reservoir to draw gas from the actuation chamber, and thus drawfluid into the pumping chamber. As can be seen in FIG. 12 , from a timeshortly after T₁ to about time T₂, a negative pressure is applied to theactuation chamber). As with the expelling (positive pressure), strokedescribed above, repeatedly reducing and increasing the flow restrictioncaused by the negative variable valve can cause the pressure beingapplied to the actuation chamber can be held at about the desirednegative control pressure, PG (which is weaker than the pressure in thenegative pressure reservoir). The pressure varies, in a sinusoidalmanner, around the desired control pressure. The actuation-chamberpressure transducer passes pressure-measurement information to thecontroller, which in turn controls the variable valve so as to cause theactuation chamber's pressure to vary around the desired controlpressure, P_(C−). If there are no fault conditions, the diaphragm ispulled against a rigid wall of the actuation chamber, thereby ending thedraw (negative pressure) stroke. As described above, the controllerdetermines that the end of stroke has been reached when the partialvacuum measured in the actuation chamber no longer drops off even thoughthe restriction created by the variable valve is reduced. In FIG. 12 ,the end of the draw stroke occurs around time T₂. When the end of strokeis sensed, the controller causes the variable valve to close completelyso that the actuation chamber's vacuum does not increase much beyond thedesired negative control pressure, P_(C−). Once the draw stroke hasended, the positive variable valve can be partially opened to begin anew expelling stroke with positive pressure.

Thus, each pod pump in this example uses the two variable-orifice valvesto throttle the flow from the positive-pressure source and into thenegative-pressure. The pressure in the actuation chamber is monitoredand a controller uses this pressure measurement to determine theappropriate commands to both valves to achieve the desired pressure inthe actuation chamber. Some advantages of this arrangement are that thefilling and delivering pressure may be precisely controlled to achievethe desired flow rate while respecting pressure limits, and that thepressure may be varied with a small sinusoidal signature command. Thissignature may be monitored to determine when the pump reaches the end ofa stroke.

Another advantage of using variable valves in this way, instead ofbinary valves, is that by only partially opening and closing thevariable valves the valves are subject to less wear and tear. Therepeated “banging” of binary valves all the way opened and all the wayclosed can reduce the life of the valve.

If the end of stroke is detected and the integrated value of thecorrelation function is very small, this may be an indication that thestroke occluded and did not complete properly. It may be possible todistinguish upstream occlusions from downstream occlusions by looking atwhether the occlusion occurred on a fill or a delivery stroke (this maybe difficult for occlusions that occur close to the end of a stroke whenthe diaphragm is near the chamber wall). FIGS. 13A-13B depict occlusiondetection (the chamber pressure drops to 0 when an occlusion isdetected).

Under normal operation, the integrated value of the correlation functionincreases as the stroke progresses. If this value remains small or doesnot increase the stroke is either very short (as in the case of a verylow impedance flow or an occlusion) or the actual pressure may not betracking the desired sinusoidal pressure due to a bad valve or pressuresignals. Lack of correlation can be detected and used for error handlingin these cases.

Under normal circumstances when the flow controller is running, thecontrol loop will adjust the pressure for any changes in flow rate. Ifthe impedance in the circuit increases dramatically and the pressurelimits are saturated before the flow has a chance to reach the targetrate, the flow controller will not be capable of adjusting the pressureshigher to reach the desired flow rate. These situations may arise if aline is partially occluded, such as when a blood clot has formed in thecircuit. Pressure saturation when the flow has not reached the targetflow rate can be detected and used in error handling.

If there are problems with the valves or the pneumatics such as aleaking fluid valve or a noisy pressure signal, ripple may continue onthe stroke indefinitely and the end of stroke algorithm may not seeenough of a change in the pressure ripple to detect end of stroke. Forthis reason a safety check is added to detect if the time to complete astroke is excessive. This information can be used for error handling.

In a dual pump, such as pump 13 in FIG. 3A, the two pump chambers may becycled in opposite directions to affect the pumping cycle. A phaserelationship from 0° (both chambers act in the same direction) to 180°(chambers act in opposite directions) can be selected. Phase movementmay be modified somewhat in certain cases because it may not be possibleto move both chambers in the same direction simultaneously; doing socould have both input or output valves open and end of stroke will notbe detected properly.

Selecting a phase relationship of 180° yields continuous flow into andout of the pod. This is the nominal pumping mode when continuous flow isdesired. Setting a phase relationship of 0° is useful for single needleflow. The pods will first fill from the needle and then deliver to thesame needle. Running at phases between 0 and 180 degrees can be used toachieve a push/pull relationship (hemodiafiltration/continuous backflush) across the dialyzer. FIGS. 8A-8C are graphical representations ofsuch phase relationships.

The pod pumps may control flow of fluid through the various subsystems.For instance, a sinusoidal pressure waveform may be added to a DCpressure command to make up the commanded pressure signal for the podpumps. When the diaphragm is moving, the pressure in the pods tracks thesinusoidal command. When the diaphragm comes in contact with the chamberwall and is no longer moving, the pressure in the pod remains constantand does not track the sinusoidal input command. This difference in thepressure signal command following of the pods is used to detect the endof a stroke. From the end of stroke information, the time for eachstroke is calculated. Knowing the volume of the pods and the time tocomplete a stroke, a flow rate for each pod can be determined. The flowrate is fed back in a PI loop in order to calculate the required DCpressure for the next stroke.

The amplitude of the sinusoidal input may be selected such it is largeenough for the actual pressure to reasonably track the command and smallenough such that when it is subtracted from the minimum DC pump pressureand applied to the pod, the pressure is sufficient to cause thediaphragm to move under expected operating conditions of fluidviscosity, head height and fluid circuit resistance. The frequency ofthe sinusoidal input was selected empirically such that it is possibleto reliably detect end of stroke. The more cycles of the sine wave perstroke, the more accurate the end of stroke detection algorithm.

To detect the change in the command following of the pod pressure, thepressure signal in the pods is sent through a cross correlation filter.The size of the sampling window for the cross correlation filter isequivalent to the period of the input sine wave. For every sample in thewindow the commanded pressure signal is multiplied by the previoussample of the actual pressure and added to the previous correlationvalue. The window is then shifted by one frame and the process isrepeated. The resulting product is then differentiated and passedthrough a second order filter with a corner frequency the same as theinput sine wave frequency and a damping ratio of one. The effect of thisfilter is to act as a band pass filter, isolating correlated signals atthe input sinusoidal frequency. The absolute value of the output of thisfilter is then passed through a second order low pass filter with thesame frequency of the sinusoidal frequency and a damping ratio of 3.0.This second filter is used integrate the differentiated signal to and toreduce noise in the resulting signal. If the two signals are correlated,the resulting filtered value will be large. If the two signals are notcorrelated (for example at end of stroke), the resulting filtered valuewill be small. The end of stroke can be detected when the filtered crosscorrelation signal drops below a particular threshold, or when thesignal drops off a by a percentage of its maximum value through out thestroke. To tune performance for a particular pumping scenario, thisthreshold or percent drop can be varied as a function of pressure orflow rate.

Since the end of stroke algorithm typically takes about one cycle of thesinusoidal ripple to detect end of stroke, minimizing this cycle time(maximizing the sine wave frequency) reduces the delay at the end ofstroke. Low pressure, high frequency flows are not well tracked by thecontroller. Lower pressure strokes tend to have lower flow rates andthus the delay at the end of stroke is a lesser percentage of the totalstroke time. For this reason, the frequency can be lower for lowpressure strokes. Frequency of the sine wave can be adjusted as a linearfunction of the delivery pressures. This insures minimum delays when thestrokes are the shortest. When the frequency of the sine wave for thedesired pressure is changed, the filters for the cross correlationfunction must also be adjusted. Filters are set up to continuouslycalculate the filter coefficients based on this changing frequency.

Pressure in the pod chambers may also be controlled using two variablesolenoid valves; one connecting the plenum to a higher pressure source,the second connecting the plenum to lower pressure (or vacuum) sink.Solenoid valves tend to have a large dead band region so a non-linearoffset term is added to the controller to compensate.

A diagram of an example control algorithm is shown in FIG. 14 . Thecontroller in this example is a standard discrete PI controller. Theoutput of the PI controller is split into two paths; one for the sourcevalve, one to the sink valve. An offset term is added to each of thesepaths to compensate for the valve dead band. The resulting command isthen limited to valves greater than zero (after being inverted in thecase of the sink valve).

The offset term is positive in the case of the source valve, andnegative in the case of the sink valve. As a result, both valves will beactive even as the error goes to zero. These offsets do improve thetrajectory following and disturbance rejection ability of thecontroller, but can also result in leakage from both valves at steadystate if the command offsets are slightly larger than the actual valvedead band. If this is the case, the valves will have equal and oppositeleakage mass flows at steady state.

To eliminate this leakage mass flow when the control system is idle, a“power save” block can be added to turn off the valves if the absolutevalue of the error term remains small for a period of time. This isanalogous to using mechanical brakes on a servomotor.

Referring now to FIG. 15 , the controller in this example uses astandard discrete PI regulator; a diagram of the PI regulator is shown.The integrator can be limited to prevent wind up when the commands aresaturated. The integrator will always be capable of unwinding. Becausethere are different amounts of air in the pod for a fill and a deliverstroke, the response of the pod can be very different for a fill anddeliver stroke. The proportional gain is adjusted differently for a filland deliver stroke to better tune for the different pod responses.

The saturation limits chosen for the PI regulator should take intoaccount the offset that will be added to the result. For example, if thevalve saturates at 12V and a 5V fixed offset will be added after the PIloop, the saturation limit in the PI loop should be set to 7V. Thispositive and negative saturation limits will likely be different due tothe different dead band in the source and sink valves.

During a fill stroke, the upstream fluid valve is closed and the downstream fluid valve is opened to allow fluid flow into the chamber.During a delivery stroke the upstream fluid valve is opened and thedownstream fluid valve is closed to allow fluid flow out of the chamber.At the end of stroke, and until the next stroke starts, both fluidvalves are closed.

As discussed, in certain aspects, a pod pump may be operated throughaction of a control fluid, for example, air, nitrogen, water, an oil,etc. The control fluid may be chosen to be relatively incompressible,and in some cases, chosen to be relatively inexpensive and/or non-toxic.The control fluid may be directed into the system towards the pumpsusing a series of tubes or other suitable conduits. A controller maycontrol flow of control fluid through each of the tubes or conduits. Insome cases, the control fluid may be held at different pressures withinthe various tubes or conduits. For instance, some of the control fluidmay be held at positive pressure (i.e., greater than atmosphericpressure), while some of the control fluid may be held at negativepressures (less than atmospheric pressure) or even zero pressure (i.e.,vacuum). As a specific, non-limiting example, a pod pump such as the oneillustrated in FIG. 11A may be controlled through operation of thecontrol fluid by the controller. As previously discussed, the controller(119) may open and close valves (e.g., valves 117 and 118) to expose thepneumatic side of the pod pump to a positive pressure (121) or a vacuumpressure (122) at different points during a pumping cycle.

In addition, in certain embodiments, the controller (typicallyelectronic) may also be kept separate from the various fluid circuits,such that there is no electronic contact between the controller and thevarious fluid circuits, although the control fluid (e.g., air) is ableto pass between the controller and the various pumps. This configurationhas a number of advantages, including ease of maintenance (thecontroller and the various circuits can be repaired independently ofeach other). In one embodiment, the fluid circuits may be heated todisinfection temperatures and/or exposed to relatively high temperaturesor other harsh conditions (e.g., radiation) to effect disinfection,while the electronic controller (which is typically more delicate) isnot exposed to such harsh conditions, and may even be kept separate byan insulating wall (e.g., a “firewall”) or the like.

Thus, in some embodiments, the system may include a “cold” section(which is not heated), and a “hot” section, portions of which may beheated, e.g., for disinfection purposes. The cold section may beinsulated from the hot section through insulation. In one embodiment,the insulation may be molded foam insulation, but in other embodimentscan be any type of insulation, including but not limited to a sprayinsulation or an insulation cut from sheets.

In some cases, the “hot” section may be heated to relatively hightemperatures, e.g., the “hot” section may be heated to temperaturessufficient to sterilize components within the “hot” section. As manyelectronics can not go above 50° C. without failing or other adverseconsequences, it may be advantageous in some embodiments to separate theelectronics from other components that may be disinfected. Thus, in somecases, the components that may need to be disinfected are kept in the“hot” section, while components that cannot be heated to suchtemperatures are kept in the “cold” section. In one embodiment, the coldsection includes a circulation system, e.g., a fan and/or a grid toallow air to flow in and out of the cold box.

All, or a portion of, the “hot” section may be encased in insulation. Insome cases, the insulation may be extended to cover access points to the“hot” section, e.g., doors, ports, gaskets, and the like. For instance,when the “hot” section is sealed, the insulation may completely surroundthe “hot” section in some cases.

Non-limiting examples of components that may be present within the“cold” section include power supplies, electronics, power cables,pneumatic controls, or the like. In some cases, at least some of thefluids going to and from the “hot” section may pass through the “cold”section; however, in other cases, the fluids may pass to the “hot”section without passing through the “cold” section.

Non-limiting examples of components that may be present within the “hot”section include cassettes (if present), fluid lines, or the like. Insome cases, some electrical components may also be included in the “hot”section. These include, but are not limited to, a heater. In oneembodiment, the heater can be used to heat the hot box itself, inaddition to fluid (see, e.g., heater 72 of FIG. 3A). In someembodiments, the heater heats the entire “hot” section to reach adesired temperature.

In one embodiment, the “hot” section includes some or all of the fluidiclines. In addition, in some cases, the “hot” section may include, but isnot limited to, temperature and conductivity sensors, blood leaksensors, heaters, other sensors, switches, emergency lights, or thelike.

In some cases, a manifold may transition from the “cold” section to the“hot” section, e.g., a manifold for air or another control fluid.

Separating the components into “hot” and “cold” sections may offerseveral advantages; those include, but are not limited to: longevity ofelectrical components, reliability, or efficiency. For example, byseparating the components into hot and cold, the entire hot box may beheated. This may allows for more efficient use of heat which leads to amore energy efficient system. This also may allow for the use ofstandard, off the shelf electronics which leads to lower cost.

In some embodiments, the control fluid used for controlling the pumps,valves, etc. is air, and the air may be brought into the system throughthe operation of one or more air compressors. In some cases, the aircompressor may be kept separate from the blood flow path and thedialysate flow path systems within the system, and air from the aircompressor may be brought to the various pumps through various tubes,conduits, pipes, or the like. For example, in one embodiment, apneumatic interface is used to direct air from the air compressor to aseries of tubes or conduits fluidically connected with the various pumpsor chambers.

A non-limiting example can be seen in FIG. 16 , which shows a schematicrepresentation of a dual-housing arrangement according to oneembodiment. This arrangement may be advantageously used with cassettesthat include many pneumatically actuated pumps and/or valves. If thenumber of pneumatically actuated pumps and/or valves in a cassette islarge enough, the cassette containing these pumps and valves can becomeso large, and the pressures involved can become so great, that it maybecome difficult to properly seal and position all of the pumps andvalves. This difficulty may be alleviated by using two or more differenthousings. The valves and pumps (such as pod pumps 42) are placed in amain housing 41, from which connecting tubes 45 lead from pneumaticports 44. The main housing 41 also has inlet and outlet tubes 43, whichallow liquid to flow into and out of the main housing. The connectingtubes 45 provide pneumatic communication between valves and pumps in themain housing 41 and a smaller, secondary tube-support housing 46, whichis provided with a pneumatic interface 47 for each of the tubes. Theproper positioning and sealing of all the pneumatic interfaces 47against receptacles in the base unit can be accomplished more easilywith the smaller tube-support housing 46 than it would be if thepneumatic actuation was applied to the larger main housing directly.

The control fluid (e.g., air) may be supplied to the system with one ormore supply tanks or other pressure sources, in one set of embodiments.For instance, if two tanks are used, one supply tank may be a positivepressure reservoir, and in one embodiment, has a set point of 750 mmHg(gauge pressure) (1 mmHg is about 133.3 pascals). The other supply tankcan be a vacuum or negative pressure reservoir, and in one embodiment,has a set point of −450 mmHg (gauge pressure). This pressure differencemay be used, for instance, between the supply tanks and the required podpressure to allow for accurate control of the variable valves to the podpumps. The supply pressure limits can be set based on maximum pressuresthat can be set for the patient blood flow pump plus some margin toprovide enough of a pressure difference for control of the variablevalves. Thus, in some cases, the two tanks may be used to supplypressures and control fluids for the entire system.

In one embodiment, two independent compressors service the supply tanks.Pressure in the tanks can be controlled using any suitable technique,for instance, with a simple bang-bang controller (a controller thatexists in two states, i.e., in an on or open state, and an off or closedstate), or with more sophisticated control mechanisms, depending on theembodiment. As an example of a bang-bang controller, for the positivetank, if the actual pressure is less then the desired pressure minus ahysteresis, the compressor servicing the positive tank is turned on. Ifthe actual pressure is greater then the desired pressure plus ahysteresis, the compressor servicing the positive tank is turned off.The same logic may be applied to the vacuum tank and control of thevacuum compressor with the exception that the sign of the hysteresisterm is reversed. If the pressure tanks are not being regulated, thecompressor is turned off and the valves are closed.

Tighter control of the pressure tanks can be achieved by reducing thesize of the hysteresis band, however this will result in higher cyclingfrequencies of the compressor. If very tight control of these reservoirsis required, the bang-bang controller could be replaced with a PIDcontroller and using PWM signals on the compressors. Other methods ofcontrol are also possible.

However, other pressure sources may be used in other embodiments, and insome cases, more than one positive pressure source and/or more than onenegative pressure source may be used. For instance, more than onepositive pressure source may be used that provides different positivepressures (e.g., 1000 mmHg and 700 mmHg), which may be used to minimizeleakage. For example, high positive pressure can be used to controlvalves, whereas lower positive pressures can be used to control pumps.This limits the amount of pressure that can potentially be sent to thedialyzer or to the patient, and helps to keep actuation of the pumpsfrom overcoming the pressures applied to adjacent valves. A non-limitingexample of a negative pressure is −400 mmHg. In some cases, the negativepressure source may be a vacuum pump, while the positive pressure pumpmay be an air compressor.

Certain aspects of the invention include various sensors; for instance,in various embodiments of the inventions described herein, systems andmethods for fluid handling may be utilized that comprise sensorapparatus systems comprising a sensor manifold. Examples of suchembodiments may include systems and methods for the diagnosis,treatment, or amelioration of various medical conditions, includingembodiments of systems and methods involving the pumping, metering,measuring, controlling, and/or analysis of various biological fluidsand/or therapeutic agents, such as various forms of dialysis, cardiacbypass, and other types of extracorporeal treatments and therapies.Further examples include fluid treatment and preparation systems,including water treatment systems, water distillation systems, andsystems for the preparation of fluids, including fluids utilizeddiagnosis, treatment, or amelioration of various medical conditions,such as dialysate.

Examples of embodiments of the inventions described herein may includedialysis systems and methods. More specifically, examples of embodimentsof the inventions described herein may include hemodialysis systems andmethods of the types described in U.S. patent application Ser. No.11/871,680, filed Oct. 12, 2007 entitled “Pumping Cassette”; or U.S.patent application Ser. No. 12/038,648 entitled “Cassette SystemIntegrated Apparatus,” filed on Feb. 27, 2008, each of which isincorporated herein by reference.

In such systems and methods, the utilization of one or more sensormanifolds may allow subject media to be moved from one environment toanother environment that is more conducive to obtaining sensor readings.For example, the cassette manifold may be contained in an area that isless subject to various types of environment conditions, such astemperature and/or humidity, which would not be preferable for sensorapparatus such as a sensing probe. Alternatively, sensing apparatus andsensing apparatus system may be delicate and may be more prone tomalfunctions than other components of a system. Separating the sensorapparatus and the sensor apparatus systems from other components of thesystem by use of a sensor manifold may allow the sensing apparatus andsensing apparatus systems to be checked, calibrated, repaired orreplaced with minimal impact to other components in the system. Theability to check, calibrate, repair or replace the sensor manifold withminimal impact to the remainder of the system may be advantageous whenutilized in connection with the integrated cassette systems and methodsdescribed in U.S. patent application Ser. No. 12/038,648 entitled“Cassette System Integrated Apparatus,” filed on Feb. 27, 2008.Alternatively, the sensor manifold may be replaced either more or lessfrequently than other components of the system.

With reference to FIGS. 53-58 , various embodiments of an exemplarysensor manifold are shown. One or more subject media, e.g., a liquid inthese exemplary embodiments, may be contained in or flow throughcassette manifold 4100. For example, one subject media may entercassette manifold 4100 via pre-molded tube connector 4101 and exit thecassette manifold via pre-molded tube connector 4102. Between tubeconnector 4101 and 4102, there is a fluid path though the cassette (bestshown as fluid path 4225 in FIG. 54 ). Likewise, fluid paths (shown asfluid paths 4223, 4220, 4222, 4224, and 4221 respectively in FIG. 54 )extend between sets of tube connectors 4103 and 4104; 4105 and 4106;4107, 4108, and 4109; 4110 and 4111; and 4112 and 4113. In certainembodiments, each fluid path may contain subject media of differentcomposition or characteristics. In other embodiments, one or more fluidpaths may contain the same or similar subject media. In certainembodiments, the same subject media may be flowed through more than oneflow path at the same time to check and/or calibrate the sensorapparatus systems associated with such fluid paths.

Referring now to FIG. 55 , in these exemplary embodiments of sensormanifold 4100 that may be used in conjunction with the sensor apparatusand sensor apparatus systems described herein, the cassette includes atop plate 4302 and a base 4301. Fluid paths, such as the fluid path 4225(as shown in FIG. 54 ) extending between tube connectors 4101 and 4102extend between the base and top plate. The cassettes may be constructedfrom a variety of materials. Generally, in the various exemplaryembodiment, the materials used are solid and non flexible. In thepreferred embodiment, the plates are constructed of polysulfone, but inother embodiments, the cassettes are constructed of any other solidmaterial and in exemplary embodiments, of any thermoplastic. Someembodiments of sensor manifold 4100 may be fabricated utilizing thesystems and methods described in U.S. patent application Ser. No.12/038,648, entitled “Cassette System Integrated Apparatus,” filed onFeb. 27, 2008.

Referring again to FIG. 55 , in these exemplary embodiments of sensormanifolds that may be used in conjunction with the sensor apparatus andsensor apparatus systems described herein, the sensor manifold 4100 mayalso include printed circuit board (PCB) 4304 and a PCB cover 4305.Various embodiments may also include connector 4303 (also shown in FIGS.53 and 56B) which may be utilized to mechanically connect the cassettemanifold 4100 to the system, such as a hemodialysis system. Cassettemanifold 4100 may also utilize various methods to hold the layers ofsensor manifold 4100 together as a unit. In various embodiments, asshown in FIG. 43 , connectors 4306 (also shown in FIG. 56B), which inone embodiment is a screw, but in other embodiments may be any means forconnection, are utilized, but any means known to one of skill in theart, such as other types of screws, welds, clips, clamps, and othertypes of chemical and mechanical bonds may be utilized.

Referring now to FIG. 56A, in exemplary embodiments of the sensormanifold 4100, tube connectors, such as tube connector 4401, is utilizedto bring subject media into or remove subject media from fluid path4402. Sensing probes, such as sensing probe 4404 extending into fluidpath 4402, are incorporated into sensor manifold 4100 so as to determinevarious properties of the subject media contained in or flowing throughthe particular fluid path in the sensor manifold. In various embodimentsone sensing probe may be utilized to sense temperature and/or otherproperties of the subject media. In another embodiment, two sensingprobes may be utilized to sense temperature and/or conductivity and/orother properties of the subject media. In yet further embodiments, threeor more sensing probes may be included. In some embodiments, one or morecombination temperature and conductivity sensing probes of the typesgenerally described herein may be utilized. In other embodiments, theconductivity sensors and temperature sensor can be any conductivity ortemperature sensor in the art. In one embodiment, the conductivitysensor elements (or sensor leads) are graphite posts. In otherembodiments, the conductivity sensors elements are posts made fromstainless steel, titanium, or any other material of the type typicallyused for (or capable of being used for) conductivity measurements. Incertain embodiments, the conductivity sensors will include an electricalconnection that transmits signals from the sensor lead to a sensormechanism, controller or other device. In various embodiments, thetemperature sensor can be any of the temperature sensors commonly used(or capable of being used) to sense temperature.

Referring again to FIG. 56A, sensing probe 4404 is electricallyconnected to PCB 4405. In certain embodiments, an electricallyconductive epoxy is utilized between sensor element 4404 and PCB 4405 toensure appropriate electrical connection, although other methods knownto those of skill in the art may be used to obtain an appropriateelectrical connection between sensor element 4404 and PCB 4405. PCB 4405is shown with edge connector 4406. In various embodiments, edgeconnector 4406 may be used to transmit sensor information from cassettemanifold 4100 to the main system. Edge connector 4406 may be connectedto a media edge connector (such as media edge connector 4601 shown inFIG. 58 ). In various embodiments, media edge connector 4601 may beinstalled in a hemodialysis machine (not shown). In such embodiments,guide tracks 4310 and 4311 (as shown in FIG. 55 ) may be utilized toassist in the connection of edge connector 4406 and media edge connector4601. Various embodiments may also include connector 4303 (as shown inFIGS. 53, 55 and 56B) which may be utilized to mechanically connect thecassette manifold 4100 to the system, such as a hemodialysis system.

Referring again to FIG. 56A, air trap 4410 is shown. In certainembodiments, an air trap, such as air trap 4410, may be utilized to trapand purge air in the system. As may be best shown in FIG. 54 , subjectmedia may flow through fluid path 4222 between tube connectors 4107 and4109 in sensor manifold 4100. As the flow of the subject media is slowedaround the turn in fluid path 4222 (near tube connector 4108), air maybe removed from the subject media through connector 4108.

Referring now to FIG. 56B, PCB cover 4305 is shown. PCB cover 4305 maybe connected to sensor manifold 4100 by connectors 4306. Edge connector4406 is also shown.

In accordance with certain embodiments, sensor manifold 4100 is passivewith respect to control of the fluid flow. In such embodiments, sensormanifold 4100 does not contain valves or pumping mechanisms to controlthe flow of the subject media. In such embodiments, the flow of thesubject media may be controlled by fluid control apparatus external tosensor manifold 4100. In other embodiments, the sensor manifold mayinclude one or more mechanical valves, pneumatic valves or other type ofvalve generally used by those of skill in the art. In such embodiments,the sensor manifold may include one or more pumping mechanisms,including pneumatic pumping mechanisms, mechanical pumping mechanisms,or other type of pumping mechanisms generally used by those of skill inthe art. Examples of such valves and pumping mechanisms may include thevalves and pumping mechanisms described in U.S. patent application Ser.No. 11/871,680, filed Oct. 12, 2007 entitled “Pumping Cassette”; or U.S.patent application Ser. No. 12/038,648, entitled “Cassette SystemIntegrated Apparatus,” filed on Feb. 27, 2008.

Referring now to FIG. 57 , tube connector 4401 is shown in base 4301.Top plate 4302 is shown, along with connector 4303. Sensing probes, suchas sensing probe 4501, extend through top plate 4302 into fluid path4503. Sensing probe 4501 may be various types of sensors, including theembodiments of sensing probes generally discussed herein.

The sensing probes, such as sensing probe 4501, may be all the same, maybe individually selected from various sensors based on the type offunction to be performed, or the same probe may be individually modifiedbased on the type of function to be performed. Similarly, theconfiguration of the fluid paths, such as the length of the fluid pathand the shape of the fluid path, may be selected based on the functionto be performed. By way of example, to detect the temperature of thesubject media in a fluid path, a temperature sensor, such as athermistor, may be used. Again, by way of example, to measure theconductivity of the subject media, one sensing probe configured tomeasure temperature and conductivity, and one sensing probe configuredonly to measure conductivity may be utilized. In other embodiments, twoor more sensing probes configured to measure both temperature andconductivity may be utilized. In various embodiments of suchconfigurations, by way of example, the second temperature sensor may bepresent but not utilized in normal operation, or the second temperaturemay be utilized for redundant temperature measurements, or the or thesecond temperature may be utilized for redundant temperaturemeasurements.

Referring again to FIG. 57 , PCB 4502 is shown with electricalconnection 4503. As further shown in FIG. 58 , PCB 4602 is shown withelectrical connection 4603 for connection to a sensing probe (shown as4501 in FIG. 45 ). PCB 4602 also contains opening 4604 for attachment totop plate (shown as 4305 in FIG. 57 ). In certain embodiments,electrical connection 4603 is mounted onto, or manufactured with, PCB4602 with air gap 4606. In such embodiments, air gap 4606 may beutilized to provide protection to the electrical connection betweensensing probe 4501 and PCB 4602 by allowing shrinking and expansion ofthe various components of sensor manifold 4100 with lesser impact to PCB4602.

Referring again to FIG. 58 , PCB 4602 is also shown with edge connector4605. As described herein, edge connector 4605 may interface with edgeconnector receiver 4601, which may be connected to the system, such asthe hemodialysis system, to which sensor manifold 4100 interfaces.

Various embodiments of exemplary sensor manifold 4100 shown in FIG.53-58 may be utilized in conjunction with hemodialysis systems andmethods described in U.S. patent application Ser. No. 11/871,680, filedOct. 12, 2007 entitled “Pumping Cassette”; or U.S. patent applicationSer. No. 12/038,648, entitled “Cassette System Integrated Apparatus,”filed on Feb. 27, 2008. In certain embodiments, sensor manifold 4100contains all of the temperature and conductivity sensors shown in FIG.59 . FIG. 59 depicts a fluid schematic in accordance with one embodimentof the inventions described in the patent applications reference above.

By way of example, in various embodiments, the temperature andconductivity of the subject media at position 4701 as shown in FIG. 59may be determined utilizing sensor manifold 4100. In such embodiments,subject media flows into tube connector 4105 (as shown in FIG. 53 )through fluid path 4220 (as shown in FIG. 54 ) and exits at tubeconnector 4106 (as shown in FIG. 53 ). The conductivity of the subjectmedia is measured by two sensing probes (not shown) extending into fluidpath 4220, at least one of which has been configured to include atemperature sensing element, such as a thermistor. The conductivitymeasurement or the temperature measurement of the subject media may beutilized to determine and/or correlate a variety of information ofutility to the hemodialysis system. For example, in various embodimentsat position 4701 in FIG. 59 , the subject media may be comprised ofwater to which a bicarbonate-based solution has been added. Conductivityof the subject media at position 4701 may be utilized to determine ifthe appropriate amount of the bicarbonate based solution has been addedprior to position 4701. In certain embodiments, if the conductivitymeasurement deviates from a predetermined range or deviates from apredetermined measurement by more than a predetermined amount, then thesubject media may not contain the appropriate concentration of thebicarbonate based solution. In such instances, in certain embodiments,the hemodialysis system may be alerted.

Again, by way of example, in various embodiments, the conductivity ofthe subject media at position 4702 as shown in FIG. 59 may be determinedutilizing sensor manifold 4100. In such embodiments, subject media flowsinto tube connector 4112 (as shown in FIG. 41 ) through fluid path 4221(as shown in FIG. 54 ) and exits at tube connector 4113 (as shown inFIG. 53 ). The conductivity of the subject media is measured by twosensing probes (not shown) extending into fluid path 4221, at least oneof which has been configured to include a temperature sensing element,such as a thermistor. The conductivity measurement or the temperaturemeasurement of the subject media may be utilized to determine and/orcorrelate a variety of information of utility to the hemodialysissystem. For example, in various embodiments at position 4702 in FIG. 59, the subject media may be comprised of water to which abicarbonate-based solution and then an acid based solution has beenadded. Conductivity of the subject media at position 4702 may beutilized to determine if the appropriate amount of the acid basedsolution (and the bicarbonate based solution in a previous step) hasbeen added prior to position 4702. In certain embodiments, if theconductivity measurement deviates from a predetermined range or deviatesfrom a predetermined measurement by more than a predetermined amount,then the subject media may not contain the appropriate concentration ofthe acid based solution and the bicarbonate based solution. In suchinstances, in certain embodiments, the hemodialysis system may bealerted.

By way of further example, in various embodiments, the temperature andconductivity of the subject media at position 4703 as shown in FIG. 59may be determined utilizing sensor manifold 4100. In such embodiments,subject media may flow into or out of tube connector 4107 (as shown inFIG. 53 ) through fluid path 4222 (as shown in FIG. 54 ) and may flowinto or out of tube connector 4109 (as shown in FIG. 53 ). As describedherein, air may be removed from the subject media as it moves past theturn in fluid path 4222. In such instances, a portion of the subjectmedia may be removed through tube connector 4108 to the drain, bringingwith it air from the air trap. The conductivity of the subject media ismeasured by two sensing probes (not shown) extending into fluid path4222, at least one of which has been configured to include a temperaturesensing element, such as a thermistor. The conductivity measurement orthe temperature measurement of the subject media may be utilized todetermine and/or correlate a variety of information of utility to thehemodialysis system. For example, in various embodiments, theconductivity measurement at position 4703 in FIG. 59 may be utilized tocorrelate to the clearance of the dialyzer. In such instances, incertain embodiments, this information may then be sent to thehemodialysis system.

Again, by way of further example, in various embodiments, thetemperature of the subject media at position 4704 as shown in FIG. 59may be determined utilizing sensor manifold 4100. In such embodiments,subject media flows into tube connector 4103 (as shown in FIG. 53 )through fluid path 4223 (as shown in FIG. 54 ) and exits at tubeconnector 4104 (as shown in FIG. 53 ). The temperature of the subjectmedia is measured by one or more sensing probes (not shown) extendinginto fluid path 4223. The temperature measurement of the subject mediaat position 4704 may be utilized to determine and/or correlate a varietyof information of utility to the hemodialysis system. For example, invarious embodiments at position 4704 in FIG. 59 , the temperature of thesubject media is determined down stream of a heating apparatus 4706. Ifthe temperature deviates from a predetermined range or deviates from apredetermined measurement by more than a predetermined amount, then thehemodialysis system may be alerted. For example in certain embodiments,the subject media may be re-circulated through the heating apparatus4706 until the temperature of the subject media is within apredetermined range.

Again, by way of further example, in various embodiments, thetemperature and conductivity of the subject media at position 4705 asshown in FIG. 59 may be determined utilizing sensor manifold 4100. Insuch embodiments, subject media flows into tube connector 4110 (as shownin FIG. 53 ) through fluid path 4224 (as shown in FIG. 54 ) and exits attube connector 4111 (as shown in FIG. 53 ). The conductivity of thesubject media is measured by two sensing probes (not shown) extendinginto fluid path 4224, at least one of which has been configured toinclude a temperature sensing element, such as a thermistor. Theconductivity measurement or the temperature measurement of the subjectmedia may be utilized to determine and/or correlate a variety ofinformation of utility to the hemodialysis system. For example, thetemperature and conductivity measurement at position 4705 may be used asa further safety check to determine if the temperature, conductivity,and, by correlation, the composition of, the subject media is withinacceptable ranges prior to the subject media reaching the dialyzer 4707and, thus, the patient. In certain embodiments, if the temperatureand/or conductivity measurement deviates from a predetermined range ordeviates from a predetermined measurement by more than a predeterminedamount, then the hemodialysis system may be alerted.

For the various embodiments described herein, the cassette may be madeof any material, including plastic and metal. The plastic may beflexible plastic, rigid plastic, semi-flexible plastic, semi-rigidplastic, or a combination of any of these. In some of these embodimentsthe cassette includes one or more thermal wells. In some embodiments oneor more sensing probes and/or one or more other devices for transferringinformation regarding one or more characteristics of such subject mediaare in direct contact with the subject media. In some embodiments, thecassette is designed to hold fluid having a flow rate or pressure. Inother embodiments, one or more compartments of the cassette is designedto hold mostly stagnant media or media held in the conduit even if themedia has flow.

In some embodiments, the sensor apparatus may be used based on a need toseparate the subject media from the sensing probe. However, in otherembodiments, the sensing probe is used for temperature, conductivity,and/or other sensing directly with subject media.

Another aspect of the invention is generally directed to methods andoperations of the systems as discussed herein. For instance, ahemodialysis system may be primed, flow-balanced, emptied, purged withair, disinfected, or the like.

One set of embodiments is generally directed to priming of the systemwith a fluid. The fluid to be primed is first directed to a dialysatetank (e.g. dialysate tank 169). Ultrafilter 73 is then first primed bypushing fluid from dialysate tank 169 to ultrafilter 73, and caused toexit line 731 through waste line 39 to the drain, as is shown by theheavy black lines in FIG. 17A. Any air present in ultrafilter 73naturally rises to the priming port and is flushed to the drain.

Next, as is shown in FIG. 17B, the balancing circuit and pump 159 of thedirecting circuit are primed by pushing fluid through the ultrafilter73, through the balancing circuit, and out to the drain. Pump 159 isprimed by running fluid forwards (through the ultrafilter to the drain).Air entering dialyzer 14 bubbles to the top of the dialyzer and leavesthrough the dialyzer exit to the drain.

Next, the blood flow pump and tubing are primed by circulating fluidthrough the blood flow circuit and the air trap back to the directingcircuit via conduit 67. As can be seen in FIG. 17C, fluid passes throughthe ultrafilter and dialyzer, forcing flow through the air trap and downthe drain. The air trap traps air circulating in the blood flow circuitand sends it to the drain. Priming can be stopped when the air sensorsstop detecting air (and some additional fluid has been passed throughthe system, as a safety margin).

Another set of embodiments is directed to adding air to the system,e.g., to empty the system of various fluids. For example, in oneoperation the dialysate tank is emptied. Vent 226 on dialysate tank 169is opened, and pump 159 is used to pump fluid from the dialysate tank tothe drain until air is detected in pump 159 (discussed below). This isshown in FIG. 19 .

Air may also be pumped into the balancing circuit in certainembodiments. This is shown in FIG. 20 . Vent 226 on dialysate 16 isopened so that air may enter the dialysate tank. Pump 159 is used topump air through the outside of ultrafilter 73. This air pressuredisplaces fluid outside the ultrafilter to the inside, then it flowsthrough the dialyzer and down the drain. During this operation, pump 159and the outside of the ultrafilter will fill with air.

In addition, air can be drawn in through the anticoagulant pump 80 intothe blood flow circuit, as is shown in FIG. 21A. The air is firstbrought into pod pumps 23 (FIG. 21A), then may be directed from the podpumps to the arterial line 203 and down the drain (FIG. 21B), or to thevenous line 204 (through dialyzer 14) and down the drain (FIG. 21C).

In one set of embodiments, integrity tests are conducted. As theultrafilter and the dialyzer may be constructed with membrane materialthat will not readily pass air when wet, an integrity test may beconducted by priming the filter with water, then applying pressurizedair to one side of the filter. In one embodiment, an air outlet isincluded on one of the blood flow pumps and thus, the pumping chambermay be used to pump air for use in the integrity test. This embodimentuses the advantage of a larger pump. The air pressure pushes all of thewater through the filter, and the air flow stops once the water has beendisplaced. However, if the air flow continues, the membrane is rupturedand must be replaced. Accordingly, the system is primed with water.First, the mixing circuit is primed first to eliminate air prior to thedialysate tank. Then the outside of the ultrafilter is primed next, asthe ultrafilter will not pass water to the balancing circuit until theoutside is primed. The balancing circuit and the dialyzer are primednext. Finally, water is pushed across the dialyzer to prime the bloodflow circuit.

The mixing circuit is primed by first pushing water with pump 183,through line 281 and bicarbonate source 28, then through each of thepumps and through line 186 to dialysate tank 169. Dialysate tank 169 isvented so air that is pushed through bubbles to the top and leavesthrough vent 226. Once air has been primed out of dialysate tank 169,the tank is filled with water, then the priming flow continues from thedialysate tank through ultrafilter 73 to the drain. This can be seen inFIG. 22A. Water is then primed as previously discussed (see FIG. 17 ).Next, the blood flow pod pumps 23 are filled with water from dialysatetank 169, as is shown in FIG. 22B, while balancing pumps 15 are emptied,as is shown in FIG. 22C.

The test is conducted by using the blood flow pump to push each chamberof water across dialyzer 14 to balancing pump chambers 15, which startempty (FIG. 22C) and are vented to the atmosphere so that they arepresent at atmospheric pressure on the dialysate side of dialyzer 14.See FIG. 22D. Each of the blood flow circuit chambers delivers using aspecific pressure and the end-of-stroke is determined to determine theflow rate.

Another integrity test is the ultrafilter flow test. In this test, thedialysate tank is filled with water, the ultrafilter is primed bypumping water from the dialysate tank through the ultrafilter and outline 731, and water is pumped through the ultrafilter, controlling flowrate, monitoring the delivery pressure required to maintain flow.

Another set of embodiments are directed to disinfection and rinsing ofthe system. This process removes any material which may have accumulatedduring therapy, and kills any active pathogens. Typically, heat is used,although in some cases, a disinfectant may be added. Water is maintainedusing the dialysate tank and replenished as necessary as water isdischarged.

A recirculating flow path is shown in FIG. 23 . The flow along this pathis essentially continuous, and uses conduits 67 to connect the bloodflow circuit with the directing circuit. The main flow path is heatedusing heater 72, which is used to increase the water temperature withinthe recirculating flow path, e.g., to a temperature that can kill anyactive pathogens that may be present. Most of the water is recirculated,although some is diverted to drain. Note that lines 48 and 731 are keptopen in this example to ensure that these lines are properlydisinfected. In addition, the flow paths through ultrafilter 73 can beperiodically selected to purge air from the ultrafilter, and/or toprovide recirculating flow through this path. Temperature sensors (e.g.,sensors 251 and 252) can be used to ensure that proper temperatures aremet. Non-limiting examples of such sensors can be seen in U.S. patentapplication Ser. No. 12/038,474, entitled “Sensor Apparatus Systems,Devices and Methods,” filed on Feb. 27, 2008, and incorporated herein byreference.

In one set of embodiments, the system is primed with dialysate asfollows. In this operation, pod pump 280 is filled with water (FIG.24A), and then water is pushed backwards through pump 183 to expel airfrom the top of bicarbonate source 28. The air is collected in pod pump282. See FIG. 24B. Next, the air in pod pump 282 is expelled through podpump 280 and line 186 to dialysate tank 169. Vent 226 in dialysate tank169 is opened so that the air can leave the system (FIG. 24C). Inaddition, acid may be pumped in from acid source 29. Bicarbonateconcentrate from bicarbonate source 28 and water are then mixed. Pump183 is used to provide water pressure sufficient to fill bicarbonatesource 28 with water, as is shown in FIG. 24D.

The acid and bicarbonate solutions (and sodium chloride solution, if aseparate sodium chloride source is present) are then metered withincoming water to prepare the dialysate. Sensors 178 and 179 are used toensure that the partial mixtures of each ingredient with water iscorrect. Dialysate that does not meet specification is emptied to thedrain, while good dialysate is pumped into dialysate tank 14.

In another set of embodiments, the anticoagulant pump is primed. Primingthe pump removes air from the heparin pump and the flow path, andensures that the pressure in the anticoagulant vial is acceptable. Theanticoagulant pump can be designed such that air in the pump chamberflows up into the vial. The test is performed by closing all of theanticoagulant pump fluid valves, measuring the external volume, chargingthe FMS chamber with vacuum, opening valves to draw from the vial intothe pumping chamber, measuring the external volume (again), charging theFMS chamber with pressure, opening the valves to push fluid back intothe vial, and then measuring the external volume (again). Changes inexternal volume that result from fluid flow should correspond to theknown volume of the pumping chamber. If the pumping chamber cannot fillfrom the vial, then the pressure in the vial is too low and air must bepumped in. Conversely, if the pumping chamber cannot empty into thevial, then the pressure in the vial is too high and some of theanticoagulant must be pumped out of the vial. Anticoagulant pumped outof the vial during these tests can be discarded, e.g., through thedrain.

In yet another set of embodiments, the system is rinsed with dialysatewhile the patient is not connected. This can be performed before orafter treatment. Prior to treatment, dialysate may be moved and aportion sent to the drain to avoid accumulating sterilant in thedialysate. After treatment, this operation rinses the blood path withdialysate to push any residual blood to the drain. The flow paths usedin this operation are similar to the flow paths used with water, asdiscussed above.

Acid concentrate may be pumped out of the mixing chamber. Pump 184 isactivated so that pod pump 280 can draw out acid from pump 184 and acidsource 29, to be mixed in line 186 and sent to the drain. Similarly,bicarbonate may be pumped out of the mixing chamber as is shown in FIG.25 . Pump 183 is used to draw water from bicarbonate source 28, then podpump 280 is used to pass the water into line 186 to the drain.

In still another set of embodiments, dialysate prime is removed from theblood flow circuit, to avoid giving the patient the priming fluid. FIGS.26A and 26B show fluid leaving each of the balancing pump chambers andbeing expelled to the drain. Next, the dialysate side of dialyzer 14 isclosed, while blood is drawn into the blood flow path from the patient(FIG. 26C). The patient connections are then occluded while the bloodflow pump chambers 23 push the priming fluid across the dialyzer to thebalancing circuit (FIGS. 26D and 26E). This fluid is then pushed todrain, as previously discussed. This operation can be repeated asnecessary until sufficient priming fluid has been removed. Afterwards,the balancing pumps are then refilled with fresh dialysate, keeping thepatient connections occluded, as is shown in FIG. 26F.

In yet another set of embodiments, a bolus of anticoagulant may bedelivered to the patient. Initially, a bolus of anticoagulant is pumpedfrom the vial (or other anticoagulant supply) to one chamber of pump 13,as is shown in FIG. 27A. The anticoagulant pump alternates betweenpumping air into the vial and pumping anticoagulant out of the vial,thereby keeping the pressure relatively constant. The remaining volumeis then filled with dialysate (FIG. 27B). The combined fluids are thendelivered to the patient down arterial line 203, as shown in FIG. 27B.In some cases, the same pump chamber may be refilled with dialysateagain (see FIG. 27B), and that volume delivered to the patient also, toensure that all of the anticoagulant has been properly delivered.

In still another set of embodiments, the system may perform push-pullhemodiafiltration. In such cases, blood flow pump 13 and balancing pumps15 can be synchronized to pass fluid back and forth across the dialyzer.In hemodiafiltration, hydrostatic pressure is used to drive water andsolute across the membrane of the dialyzer from the blood flow circuitto the balancing circuit, where it is drained. Without wishing to bebound by any theory, it is believed that larger solutes are more readilytransported to the used dialysate due to the convective forces inhemodiafiltration.

In one set of embodiments, solution infusion may be used to deliveryfluid to the patient. As is shown in FIG. 28 , pump 159 in the directingcircuit is used to push fluid across dialyzer 14 into the blood flowcircuit, which thus causes delivery of fluid (e.g., dialysate) to thepatient.

According to another set of embodiments, after repeated use, thedialyzer can lose its efficiency or even the ability to function at allas a result of compounds adhering to and building up on the membranewalls in the dialyzer. Any standard measure of dialyzer clearancedetermination may be used. However, one method of measuring how muchbuild-up has accumulated in the dialyzer, i.e., how much the dialyzer'sclearance has deteriorated, a gas is urged into the blood side of thedialyzer, while a liquid is held on the dialysate side of the dialyzer.By measuring the volume of gas in the dialyzer, the clearance of thedialyzer may be calculated based on the volume of gas measured in thedialyzer.

Alternatively, in other embodiments, because of the pneumatic aspects ofthe present system, clearance may be determined as follows. By applyinga pressure differential along the dialyzer and measuring the flow rateof the dialyzer, the clearance of the dialyzer may then becorrelated/determined or calculated, based on the pressure differentialand the flow rate. For example, based on a known set of correlations orpre-programmed standards including a correlation table or mathematicalrelationship. For example, although a look-up table may be used, or adetermined mathematical relationship may also be used.

The dialyzer's clearance can also be measured using a conductivity probein the blood tube plug-back recirculation path. After treatment thepatient connects the blood tubes back into the disinfection ports. Thefluid in the blood tubes and dialyzer may be recirculated through thesedisinfection port connections, and the conductivity of this solution maybe measured as it passes through the conductivity measurement cell inthis recirculation path.

To measure the dialyzer clearance, pure water may be circulated throughthe dialysate path and the conductivity of the fluid flowing through theblood recirculation path is continuously monitored. The pure water takesions from the solution in the blood flow circuit recirculation path at arate which is proportional to the clearance of the dialyzer. Theclearance of the dialyzer may be determined by measuring the rate atwhich the conductivity of the solution in the blood flow circuitrecirculation path changes.

The dialyzer's clearance can be measured by circulating pure water onone side and dialysate on the other, and measuring the amount of fluidpassing through the dialyzer using conductivity.

In one set of embodiments, in case of a power failure, it may bedesirable to return as much blood to the patient as possible. Since oneembodiment of the hemodialysis system uses compressed gas to actuatevarious pumps and valves used in the system, a further embodiment takesadvantage of this compressed gas to use it in case of power failure toreturn blood in the system to the patient. In accordance with thisprocedure and referring to FIG. 29A, dialysate is pushed across thedialyzer 14, rinsing blood residing in the blood flow circuit 10 back tothe patient. Compressed gas (which in a preferred embodiment iscompressed air) can be used to push dialysate across the dialyzer 14. Avalve 77 releases the compressed air to initiate this function. Thismethod may be used in situations where electrical power loss or someother failure prevents the dialysis machine from rinsing back thepatient's blood using the method normally employed at the end oftreatment.

As compressed air is used to increase the pressure on the dialysate sideof the dialyzer 14 and force dialysate through the dialyzer to the bloodside, thereby pushing the patient's blood back to the patient, thepatient, or an assistant, monitors the process and clamps the tubesbetween the blood flow circuit and the patient once adequate rinse backhas been achieved.

In one embodiment, a reservoir 70 is incorporated into the hemodialysissystem and is filled with compressed air prior to initiating treatment.This reservoir 70 is connected to the dialysate circuit 20 through amanually actuated valve 77. When the treatment is finished or aborted,this valve 77 is opened by the patient or an assistant to initiate therinse-back process. The membrane of the dialyzer 14 allows dialysate topass through, but not air. The compressed air displaces dialysate untilthe patient tubes are clamped, or the dialysate side of the dialyzer isfilled with air.

In another embodiment, a reservoir containing compressed air is providedas an accessory to the dialysis machine. If the treatment is terminatedearly due to a power failure or system failure of the dialysis machine,this reservoir may be attached to the dialysate circuit on the machineto initiate the rinse-back process. As in the previous embodiment, therinse-back process is terminated when the patient tubes are clamped, orthe dialysate side of the dialyzer is filled with air.

In yet another embodiment shown in FIG. 29B, an air reservoir 70 isincorporated into the system and attached to a fluid reservoir 75 with aflexible diaphragm 76 separating the air from the dialysate fluid. Inthis case, the compressed air pushes the diaphragm 76 to increase thepressure in the dialysate circuit 20 rather than having the compressedair enter the dialysate circuit. The volume of the dialysate that isavailable to be displaced is determined by the volume of the fluidchamber 75. The rinse-back process is terminated when the patient tubesare clamped, or when all of the fluid is expelled and the diaphragm 76bottoms out against the wall of the fluid chamber 75.

In any of these embodiments, the operation of the systems or methods maybe tested periodically between treatments by running a program on thedialysate machine. During the test the user interface prompts the userto actuate the rinse-back process, and the machine monitors the pressurein the dialysate circuit to ensure successful operation.

In the systems depicted in FIGS. 29A and 29B, blood is drawn from thepatient by the blood flow pump 13, pushed through the dialyzer 14 andreturned to the patient. These components and the tubing that connectsthem together make up the blood flow circuit 10. The blood contained inthe blood flow circuit 10 should be returned to the patient when thetreatment is finished or aborted.

The dialysate solution is drawn from the dialysate tank 169 by thedialysate pump 159, and passed through the heater 72 to warm thesolution to body temperature. The dialysate then flows through theultrafilter 73 which removes any pathogens and pyrogens which may be inthe dialysate solution. The dialysate solution then flows through thedialyzer to perform the therapy and back to the dialysate tank.

The bypass valves 74 may be used to isolate the dialyzer 14 from therest of the dialysate circuit 20. To isolate the dialyzer 14, the twovalves connecting the dialysate circuit 20 to the dialyzer are closed,and the one shunting dialysate around the dialyzer is opened.

This rinse-back procedure may be used whether or not the dialyzer 14 isisolated and is used when the treatment is ended or aborted. Thedialysate machine is turned off or deactivated so the pumps are notrunning. When the patient is ready for rinse-back, air valve 77 isopened by the patient or an assistant. The air in the compressed airreservoir 70 flows toward the dialysate circuit 20, increasing thepressure on the dialysate side of the dialyzer 14. This increase inpressure may be achieved by allowing the air to enter the dialysatecircuit directly, as shown in FIG. 29A or indirectly by pushing on thediaphragm 76 shown in FIG. 29B.

The air pressure on the dialysate side of the dialyzer forces somedialysate solution through the dialyzer 14 into the blood flow circuit.This dialysate solution displaces the blood, rinsing the blood back tothe patient. The patient or an assistant can observe the rinse processby looking at the dialyzer 14 and the blood tubes. The dialysatesolution starts in the dialyzer, displacing the blood and making itappear much clearer. This clearer solution progresses from the dialyzertoward the patient. When it reaches the patient the blood tube clamps 71are used to pinch the tubing to terminate the rinse-back process. If oneline rinses back sooner than the other the quicker line may be clampedfirst and the slower line may be clamped later.

Once the rinse-back is completed and the blood lines are clamped thepatient may be disconnected from the dialysis machine.

The implementation of one embodiment of the system and method is shownin FIG. 29A takes advantage of the hydrophilic nature of the materialused to make the tiny tubes in the dialyzer 14. When this material iswet, the dialysate solution can pass through but air cannot. Where theembodiment shown in FIG. 29A is implemented, air may enter the dialyzer14 but it will not pass across to the blood flow circuit 10.

In either implementation, the volume of dialysate that may be passedthrough the dialyzer 14 is limited. This limitation is imposed by thesize of the compressed air reservoir 70, the volume of dialysatesolution contained in the dialyzer 14 and in the case of theimplementation shown in FIG. 7B the size of fluid reservoir 75. It isadvantageous to limit the volume of dialysate that may be pushed acrossthe dialyzer because giving too much extra fluid to the patientcounteracts the therapeutic benefit of removing fluid during thetherapy.

In another embodiment, in a loss of power, the air pressure to movedialysate from the dialysate circuit through the dialyzer can be derivedfrom a pressurized air reservoir that normally powers the membrane pumpsand also provides a pressure source for FMS measurements. As shown inFIG. 80 , for example, this source of air pressure can be accessed viathe FMS pathway 170 used to monitor the dialysate tank 169. In anembodiment, the manifold valves that direct air pressure or vacuum tothe various pumps and valves in the liquid flow paths of thehemodialysis machine are electrically operated. In some embodiments, thevalves in the liquid flow paths of the hemodialysis machine canthemselves be electrically actuated. In the absence of electrical power,they can be chosen or pre-set to have default open or closed positions.If the default position of a manifold valve is closed, for example, thenno air pressure (or vacuum) can be transmitted to its target. Similarly,if the default position of a manifold valve is open, then the pressureor vacuum source to which it is connected can pressurize the downstreamdevice (such as a membrane-based pump, a membrane-based valve, oranother type of valve). If a valve that directly controls flow in aliquid flow path is itself electrically actuated, the valve can bechosen to have a default position either to close off or to open itsrespective flow path. In the example illustrated in FIG. 80 , byconfiguring the manifold valve 170 a and the FMS valve 170 b to have adefault open position, for example, pressure from a pressurized air tankcan be transmitted to the dialysate tank 169. By configuring variousother manifold valves to the appropriate default positions, thecorresponding flow path valves controlled by the manifold valves can bemade to open a pathway from the dialysate tank 169, through the outerdialysate pump circuit 159, the ultrafilter 73, a portion of thebalancing circuit 143, and ultimately to the dialyzer 14. Thus, in theabsence of electrical power, and if the blood flow side of the dialyzer14 offers no impedance, dialysate from the dialysate tank 169 can bemade to flow to the dialyzer 14, allowing for rinseback of blood. Duringnormal dialysis, the control software can ensure that there is asufficient supply of dialysate in the dialysate tank 169 to allow forthe rinseback of all of the blood residing in the blood tubing set.

In alternative embodiments, if the valves that directly control flow inthe dialysate flow paths between the dialysate tank and the dialyzer arethemselves electrically actuated, they can be chosen to have an opendefault position. Conversely, other valves that control flow in pathwaysthat divert flow away from the dialyzer can be selected to have adefault closed position.

For example, in FIG. 80 , the default configuration for the appropriatemanifold valves can cause the inlet and outlet valves 171 of the outerdialysate pump circuit 159, and the balancing circuit valves 172 toremain in an ‘open’ position, providing a flow path to the dialyzer 14.Conversely, the inlet feed valve 173 a and the recirculation valve 173 bof the dialysate tank 169, and the drain valve 174 of the ultrafilter 73can be made to have ‘closed’ default positions in an unpowered state, toprevent the dialysate from being pushed to drain. In addition, the inletvalves 175 of the inner dialysate pump circuit 15 and the inlet valve176 of the bypass or ultrafiltration pump circuit 35 can be made to have‘closed’ default positions to prevent dialysate flow into those pathwaysfrom the dialyzer 14 in an unpowered state.

In order to avoid uncontrolled rinseback, the arterial supply and venousreturn lines of the blood tubing set can be compressed by an occludermechanism that maintains a default ‘occluded’ position in the absence ofpower, and that is moved to an ‘unoccluded’ position during normaldialysis. The occluder can be positioned to simultaneously occlude boththe arterial line before it reaches the blood pump cassette, and thevenous line after exiting from the dialyzer or an air bubble trap. In apreferred embodiment, before rinseback is allowed, a patient, operatoror assistant withdraws the arterial line from the patient's vascularaccess site when a rinseback is planned or a power-loss relatedrinseback is initiated. A suitable connector (such as a needle orneedle-less spike, or Luer lock connector) is placed on the end of thearterial line, and is then connected to an air trap (such as air trap19) in the venous return line. This helps to prevent any air caught inthe blood flow path at the top of the blood pump cassette or the top ofthe dialyzer from being inadvertently rinsed back toward the patient'svascular access. Once the arterial line is connected to the air trap,the patient, operator or assistant may then manually move the occluderto an ‘unoccluded’ position, decompressing the venous return line andallowing the pressurized dialysate from the dialysate circuit to pushthe blood in the blood tubing set toward the patient's vascular access.If the patient observes air in the venous line downstream from the airtrap, he or she may simply re-engage the occluder and stop the rinsebackprocess.

Although the above rinseback procedures are described with dialysate asthe solution that ultimately moves the blood in the blood flow pathtoward the patient's vascular access, any electrolyte solution that isphysiologically compatible and can safely be mixed with blood can beused in a rinseback procedure. Furthermore, rinseback technology neednot be limited to a dialysis system. Any system that circulates apatient's blood extracorporeally could potentially benefit from anemergency rinseback system and method. It would therefore be possible tointroduce a filter having a semipermeable membrane (such as a dialyzeror ultrafilter) into the blood flow path of the extracorporeal system.The other side of the semipermeable membrane would then be exposed to anelectrolyte solution in a flow path that can be pressurized by acompressed gas source with which it is in valved communication.

Another aspect of the invention is generally directed to a userinterface for the system. The user interface may be operated by anindividual, such as the patient, a family member, assistant,professional care provider, or service technician, to input options,such as treatment options, and to receive information, such asinformation about the treatment protocol, treatment status, machinestatus/condition, and/or the patient condition. The user interface maybe mounted on the treatment device and controlled by one or moreprocessors in the treatment device. In another embodiment, the userinterface may be a remote device that may receive, transmit, or transmitand receive data or commands related to the treatment protocol,treatment status, and/or patient condition, etc. The remote device maybe connected to the treatment device by any suitable technique,including optical and/or electronic wires, wireless communicationutilizing Bluetooth®, RF frequencies, optical frequencies, IRfrequencies, ultrasonic frequencies, magnetic effects, or the like, totransmit and/or receive data and/or commands from or to the treatmentdevice. In some cases, an indication device may be used, which canindicate when data and/or a command has been received by the treatmentdevice or the remote device. The remote device may include input devicessuch as a keyboard, touch screen, capacitive input device, or the liketo input data and/or commands to the treatment device.

In some embodiments, one or more processors of the treatment device mayhave a unique identification code, and the remote device may include thecapability to read and learn the unique identification code of thetreatment. Alternatively, the user can program in the uniqueidentification code. The treatment device and the remote device may usea unique identification code to substantially avoid interference withother receivers, including other treatment device.

In one set of embodiments, the treatment device may have one or moreprocessors that are connected to a web-enabled server and the userinterface device may be run on this web-enabled server. In oneembodiment, the device uses an external CPU (e.g., a GUI, graphical userinterface) to communicate via Internet protocol to the embedded webserver in or connected to the treatment device. The web page may beserved up inside the device and the GUI may communication directly via802.11b or other such wired or wireless Ethernet equivalent. The GUI maybe operated by an individual, such as the patient, a family member,assistant, professional care provider, or service technician, to inputoptions, such as treatment options, and to receive information, such asinformation about the treatment protocol, treatment status, machinestatus/condition, and/or the patient condition.

In another embodiment, the embedded web server in or connected to thetreatment device may communicate to an appropriate site on the Internet.The Internet site may require a password or other user identification toaccess the site. In another embodiment, the user may have access todifferent information depending on the type of user and the accessprovider. For example, a patient or professional caregiver may have fullaccess to patient treatment options and patient information, while afamily member may be given access to certain patient information, suchas the status and duration remaining for a given treatment or frequencyof treatments. The service technician, dialysis center, or treatmentdevice provider may access other information for troubleshooting,preventive maintenance, clinical trials, and the like. Use of theweb-enabled server may allow more than one individual to access patientinformation at the same time for a variety of purposes.

The use of a remote device, e.g., via wired or wireless communication,Internet protocol, or through an Internet site utilizing a web enabledserver, could allow a dialysis center to more effectively monitor eachpatient and/or more efficiently monitor a larger number of patientssimultaneously. In some embodiments, the remote device can serve as anocturnal monitor or nocturnal remote alert to monitor the patientduring nocturnal dialysis treatment and to provide an alarm if thepatient's condition does not meet certain parameters. In some cases, theremote device may be used to provide alarms to the patient, a familymember, assistant, professional care provider, or service technician.These alarms could alert an individual to certain conditions such as,but not limited to, a fluid leak, an occlusion, temperature outsidenormal parameters, and the like. These alarms may be audible alarms,visual alarms, and/or vibratory alarms.

An exemplary embodiment of a user interface/treatment device combinationis shown in FIG. 60 . In particular, FIG. 60 shows a perspective view ofan exemplary hemodialysis system 6000 comprising a dialysis unit 6001and a user interface unit 6002. In this embodiment, the dialysis unit6001 comprises a housing 6004 that contains suitable components forperforming hemodialysis. For example, the dialysis unit 6001 may includethe mixing circuit 25, blood flow circuit 10, balancing circuit 143 andexternal or outer dialysate circuit 142 described, for example, inconnection with FIG. 2A. The dialysis unit 6001 may also include allpatient access connections and dialysate fluidic connections needed foroperation of the system 6000.

The user interface unit 6002 comprises a user interface 6003 that auser, such as a hemodialysis patient, may use to control operation ofthe dialysis unit 6001 via a connection 6006. The connection 6006 maycomprise any suitable data connection such as a bus, a wirelessconnection, a connection over a local area network (e.g., an Ethernetlocal area network), and/or a connection over a wide area network (e.g.,the Internet). The user interface unit 6002 further comprises a housing6005 that contains components for enabling operation of the userinterface. In the example of FIG. 60 , the user interface 6003 comprisesa display screen with a touch sensitive overlay to allow touch controland interaction with a graphical user interface presented on the screen.However, many other types of user interfaces are possible, such as ascreen with a separate input mechanism, such as a keyboard and/orpointing device. The user interface 6002 may also include otherfeatures, such as push buttons, a speaker, a microphone for receivingvoice commands, and so on.

While the hemodialysis system 6000 of FIG. 60 comprises a user interfaceunit 6002 remote from and physically coupled to a dialysis unit 6001,many alternative arrangements are possible. For example, the userinterface unit 6002 may be mounted to or within dialysis unit 6001. Forconvenience, a user interface unit 6002 so mounted may be moveable fromits mount for use in different locations and positions.

FIG. 61 shows an exemplary hardware configuration for each of thedialysis unit 6001 and the user interface unit 6002. Each of these iscontrolled by a separate CPU, allowing for the separation of time andsafety critical software from the user experience software. Once atherapy has begun, it can be completed even if the user interfacecomputer fails or is disconnected. This can be supported by having somephysical control buttons and indicator lights redundant to thoseimplemented by the user interface unit 6002 and connected to the controlprocessor of the dialysis unit 6001. The dialysis unit 6001 comprises anautomation computer (AC) 6106 that controls hardware actuators andsensors 6107 that deliver and monitor hemodialysis-related therapy. Theautomation computer 6106 comprises a control unit 6108 that includes aprocessing unit 6109 and computer readable media 6110. The processingunit 6109 comprises one or more processors that may execute instructionsand operate on data stored on the computer readable media 6110. The datamay, for example, relate to hemodialysis processes that have been or maybe performed on a patient. The system architecture provides theautomation computer 6106 with software accessible safety sensors 6107and the ability to command a fail-safe state (allowing for suspension ordiscontinuation of therapy in a safe manner). A parallel independentsemiconductor device-based system can perform checks similar to thosecontrolled by the software in order to provide a redundant safetysystem. This cam be implemented, for example in a field-programmablegate array (“FPGA”), and it can also command a fail-safe stateindependently of the software system if one or more safety checks is notsatisfied. The integrity of the pneumatic, hydraulic and electricalsystems can be checked both during and between treatment sessions. Theinstructions may comprise, for example, an operating system (e.g.,Linux), application programs, program modules, and/or other encodedinstructions that perform particular processes.

The computer readable media 6110 may comprise any available media thatcan be accessed by the processing unit 6109. For example, computerreadable media 6110 may comprise computer storage media and/orcommunication media. Computer storage media may include any one or moreof volatile and/or nonvolatile memory and removable and/or non-removablemedia implemented in any method or technology for storage ofinformation, such as computer readable instructions, data structures,program modules or other data. Examples of such computer storage mediaincludes, but is not limited to, RAM, ROM, solid state disks, EEPROM,flash memory or other memory technology, CD-ROM, digital versatile disks(DVD) or other optical disk storage, magnetic cassettes, magnetic tape,magnetic disk storage or other magnetic storage devices, or any othermedium which can be used to store the desired information and which canbe accessed by the processing unit 6109. Communication media typicallyembodies computer readable instructions, data structures, programmodules or other data in a modulated data signal, such as a carrier waveor other transport mechanism, and includes any information deliverymedia. The term “modulated data signal” means a signal that has one ormore of its characteristics set or changed in such a manner as to encodeinformation in the signal. By way of example, communication media mayinclude wired media, such as a wired network or direct-wired connection,and/or wireless media, such as acoustic, RF, infrared and other wirelessmedia.

The various components of the automation computer 6106, including thecomputer readable media 6110 and the processing unit 6109, may beelectrically coupled via a system bus. The system bus may comprise anyof several types of bus structures including a memory bus or memorycontroller, a peripheral bus, and a local bus using any of a variety ofbus architectures. By way of example, such architectures may includeIndustry Standard Architecture (ISA), Micro Channel Architecture (MCA),Enhanced ISA (EISA), Video Electronics Standards Associate (VESA), andPeripheral Component Interconnect (PCI).

The automation computer 6106 may further include a universal serial bus(USB) interface 6113 so that various input and/or output devices may becoupled to the control unit 6108. Examples of such input and/or outputdevices include a monitor, speakers, a printer, a keyboard, a pointingdevice (e.g., a mouse), a scanner, personal digital assistants, amicrophone and other peripheral devices. USB is merely one exemplarytype of interface that may be used to connect peripheral devices. Otherinterfaces may alternatively be used.

As discussed above, dialysis unit 6001 includes components forperforming and monitoring hemodialysis processes. Such componentsinclude sensors and actuators 6107. To couple the control unit 6108 tothe sensors and actuators 6107, the automation computer may include ahardware interface 6111. The hardware interface 6111 may provide inputsto and receive outputs from the sensors and actuators 6107.

Automation computer 6106 may further comprise a network interface 6112to allow the computer to connect with networked devices, such as thosewithin a local area network (LAN) and/or a wide area network (WAN). Forexample, the network interface 6112 may allow the dialysis unit 6001 toexchange data with the user interface unit 6002 over a network 6114,which may comprise a LAN, such an Ethernet LAN, and/or a WAN, such asthe Internet, and may be wired or wireless. Of course, the dialysis unit6001 may alternatively or additionally exchange data with the userinterface unit 6002 over a bus or other data connection.

The user interface unit 6002 comprises a user interface computer 6119that controls a user interface, such as graphical user interface 6115that displays information to and receives inputs from the user. Like theautomation computer 6106, the user interface computer 6119 comprises acontrol unit 6116 having a processing unit 6117 and computer readablemedia 6118, a USB interface 6121 and a network interface 6120, each ofwhich may be the same as or similar to their counterparts in theautomation computer 6119. In addition, the user interface computer 6119may include a graphics interface 6122 to couple the control unit 6116 tothe graphical user interface 6115. In a preferred implementation, theuser interface computer 6119 software is not tasked to interpret datareceived from the automation computer 6106, but rather is tasked todisplay the data in a user-friendly manner.

FIG. 62 schematically shows various exemplary software processes thatmay execute on the processing units 6109 and 6117 of automation computer6106 and user interface computer 6119, respectively. The processes shownmay be launched and monitored by an executive process. For example, theAC processing unit 6109 and UIC processing unit 6117 may respectivelyinclude AC Executive 6201 and the UIC Executive 6207 to launch theprocesses within the given processing unit and provide a communicationsmechanism to determine the running status of the child processes. Theexecutives monitor each child process to ensure that each starts asexpected and continues to run. In particular, the AC Executive 6201 andthe UIC Executive 6207 may detect hung processes. When a child processterminates or fails, each executive process may take appropriate actionto ensure that the system continues to operate in a safe manner. Thismay involve terminating processes and informing the UIC executive 6207,leading to system shutdown, or restarting processes that are notsafety-critical. On the UIC processor, this may entail informing theoperator and allowing the treatment to be completed using the hard-keys.The AC Executive 6201 and the UIC Executive 6207 may use a Linuxparent-child process relationship to receive notifications from theoperating system about the termination of child processes. This allowshandling of anomalous process terminations as well as expectedterminations during a power-off sequence. The automation computer 6106and the UIC Executives 6201 and 6207 may have a message interfacebetween them to share information about their running processes. Thestatus information may be shared on a periodic basis to allow a coherentview of state of all system processes on both processor units 6109 and6117. The AC executive 6201 controls a watchdog signal to theelectronics, allowing it to place the machine in a fail-safe state whenany child process becomes unresponsive or requests a fail-safe state.Preferably, this control does not require an Input/Output server, butcan occur directly via a hardware register.

As shown in the example of FIG. 62 , the AC processing unit 6109includes an I/O Server Process 6205. The I/O Server Process 6205directly accesses hardware, such as sensors and actuators, of thedialysis unit, and provides an interface to allow other processes torequest read and write operations. For example, the I/O Server Process6205 may provide an interface for the Machine Controller 6202 to readfrom and write to the sensors and actuators, thereby isolating theMachine Controller from the details of the hardware. In the embodimentdescribed, only the Machine Controller 6202 may communicate with the I/OServer Process 6205. The interface may be a synchronous message queue.

The Machine Controller 6202, mentioned above, serves as an interface forcontrolling machine operations and reporting machine operational status.In particular, the Machine Controller 6202 implements controllers thatread sensors and set actuators via the I/O Server Process 6205. Thesecontrollers are designed to allow functions (e.g., pumping and heating)to be programmed with a variety of parameters (e.g., flow rates, phases,pressures, and temperatures) in order to support the varioushemodialysis therapies that may be performed. The configuration of thecontrollers may be established by state machines that implementhigh-level machine functions, such as priming and disinfection. Thestate machines configure flow paths and controller set points based onthe capabilities of the machine and the high level commands receivedfrom the Therapy Applications 6203, described below. The MachineController 6202 may also perform safety cross checks on various sensorsto maintain a safe, effective therapy. Machine status and healthinformation may be recorded by the Machine Controller 6202 to adatabase.

The Therapy Applications 6203 drive the patient's therapy by commandingthe Machine Controller 6202 to perform individual operations relating tohemodialysis processes. In particular, the Therapy Applications 6203 mayrun state machines that implement therapies and control the modes of thesystem. The state machines may, for example, control priming the systemwith dialysate, connecting the patient to the machine, dialyzing thepatient, rinsing the patient's blood back to their body, cleaning themachine, disinfecting the machine, running tests on the machinecomponents, replacing old or worn out components, and waiting for thepatient to return for their next treatment. The Therapy Applications6203 issue commands to and request status information from the MachineController 6202 in order to implement the therapy operations. In orderto obtain patient, therapy and machine information the TherapyApplications 6203 may interface with a database to access informationand store treatment status information. The Therapy Applications 6203may be used as an interface by the User Interface Model 6206 process,discussed below, to forward user selections and report therapy statusback to the user interface. The Therapy Applications 6203 implementsstate machines that include treatment preparation, patient connection,dialysis, solution infusion, patient disconnect, recycle preparation,disinfect, rinse, and disposable replacement. The Therapy Applications6203 process also contains a master control module responsible forsequencing the activity of all other therapy applications that preparefor and deliver daily treatment.

Like the Therapy Applications 6203, the User Interface (UI) Model 6206runs on the AC processing unit 6109. The UI Model 6206 aggregatesinformation describing the current state of the system and patient, andsupports changes to the state of the system via operator input. The UIModel 6206 separates the content of the user interface display fromnon-content related aspects (e.g., presentation) by allowing the contentof the user interface to change without affecting the underlyingsoftware that controls the user interface display. Thus, changes to theUI Model 6206 may be made without affecting the visual experienceprovided by the user interface. The UI Model 6206 does not have adisplay directly associated with it; rather, it commands the GUI 6115 ofthe user interface unit 6002 (FIG. 61 ) to display screens and returninformation. For example, when a user navigates to a new screen, the UIModel 6206 may send information to the user interface unit 6002 to beused in generating the new screen. The UI Model 6206 may also validateuser data received from the user interface unit 6002 and, oncevalidated, and forward the user data or commands based thereon to theTherapy Applications 6203.

To create the interactive displays for the GUI 6115 of the userinterface unit 6002 (FIG. 61 ), the UI View Process 6208 runs on the UIprocessor 6117 of the user interface computer. The UI View Process 6208need not keep track of screen flow or therapy state. Instead the UI ViewProcess 6208 may receive from the UI Model 6206 running on the ACprocessing unit 6109 information specifying what and how to display thecurrent state of a treatment to the user, as well as what may be input.As a result, the GUI 6115 may terminate and restart without impactingthe system's operation. In addition, the GUI 6115 need not beresponsible for validating user inputs. All inputs and commands receivedby the UI View 6208 may be sent to and validated by the UI Model 6206.Thus, all safety-critical aspects of the user interface may be handledby the UI Model 6206. Certain processes, such as those notsafety-related, do not require the participation of the UI Model 6206.For example, allowing access to information stored in a database on theuser interface computer may not require any functions to be performed bythe UI Model 6206.

Also running on the UI processor 6117, a Remote Access Application 6210provides an interface for external equipment. For example, the RemoteAccess Application 6210 may provide an interface for therapy monitoring,remote service, online assistance, and other external services, whenauthorized by a user. The Remote Access Application 6210 may beresponsible for initiating a remote connection, validating the access,and supporting the communication from the remote site to the UI Model6206.

A Database Access Application 6209 stores data to and retrieves datafrom one or more databases which may, for example, be located on theuser interface computer 6119 (FIG. 61 ). The Database Access Application6209 allows for record storage and retrieval, and provides a commonaccess point for information required by the system, such asprescription, schedule, and history information. The Database AccessApplication 6209 may also manage database files to ensure they arebacked up periodically.

As discussed in connection with FIG. 62 , the functionality of the userinterface software may be divided between the AC processing unit 6109and the UIC processing unit 6117. The UI Model 6206 and UI Controller6204 may cooperate to isolate the control of the UI data and stateinformation on the automation computer 6106 so that software and screendesign changes to the UI View 6208 will only affect thenon-safety-critical software on the user interface computer 6119. Thus,while the UI Model 6206 may be tested and run at a safety-criticallevel, the UI View 6208 may run as a non-safety-critical process.

In general, therapy and machine state information displayed on the userinterface computer 6119 originates only from the UI Model 6206.According to one exemplary embodiment, all data displayed on the userinterface computer 6119 originates from the UI Model 6206, is takendirectly from a database layer, or is temporary editing data entered bya user. The only local state information displayed or stored in the UIView 6208 may be this temporary editing data and details that allow forthe local rendering of the information. In this manner, the UI Model6208 may maintain and control the display of all validated data.Non-safety related data may be handled solely by the UI View 6208, ifdesired. For example, changes in the display language, or other displaychanges that do not impact safety-related content, may be performedusing the UI View 6208 without any effect on the UI Model 6206.

It should be appreciated that the software processes shown in FIG. 62and their association with processing units 6109 and 6117 representsjust one example of a software configuration for performing thefunctions described above. The processes may be distributed in variousalternative manners among processing units 6109 and 6117 and/or otherlocal or remote processors. Further, not all processes may be requiredin the hemodialysis system. Certain processes may be omitted or modifiedwhile maintaining the functionality of a hemodialysis system.

FIG. 63 shows an example of how information relating to the userinterface may flow between and among the hardware and softwarecomponents of the user interface computer 6119 and automation computer6106. Information may flow and be handled so that safety-criticalinformation is processed only at or below the UI Model layer.Safety-critical information relates to operations of the hemodialysissystem. For example, safety-critical information may comprise a state ofa dialysis process, a screen state of the graphical user interface,and/or the algorithms for implementing or monitoring therapies. In somecases, safety-critical information may be displayed by the graphicaluser interface. In such cases, the safety-critical information maycomprise content that is material to the operations of the hemodialysissystem. Non safety-critical information displayed by the user interfacemay comprise aspects of the display that relate to visual presentationand are not material to the operations of the hemodialysis system.

As shown in FIG. 63 , the UI Model 6206, UI Controller 6204 and TherapyApplications 620, discussed in the connection with FIG. 62 , run on theautomation computer 6106. The UI View 6208 runs on the user interfacecomputer 6119, along with Auxiliary Applications 6301. A database 6302,or an interface thereto (e.g., a database server) may also reside on theuser interface computer 6119. The UI Model 6206 aggregates theinformation describing the current state of the system and patient, andcommands the graphical user interface to display screens and returninformation. It validates and forwards user data and commands to thetherapy applications in order to give the user control over the system.The UI Model 6206 keeps the content of the user interface independentfrom the display. The graphical user interface preferably does notmaintain machine state information, allowing the user interface to bechanged or temporarily disconnected without affecting the underlyingsoftware. Although the graphical user interface is not responsible forvalidating user inputs, it may constrain ranges of various inputs, thevalidation being the responsibility of the UI Model 6206.

Considering first the flow of information between the UI View 6208 andUI Model 6206, the UI View operates as a client of the UI Model, asexplained below. The UI View 6208 requests the current screen state fromthe UI Model 6206, and the UI Model answers the request. The answerdictates the major screen state of the UI View 6208. The UI Model 6206may publish data and state information in sufficient detail so that theUI View 6208 can present various subsets of display informationaccording to a level of detail requested by a user. For example, the UIView 6208 could present the same therapy state as either a summary or astep-by-step guide using the same information from the UI Model 6206.The presentation of the information may be based, for example, on a modeselected by a user (e.g., “expert” or “novice”). The UI Model 6206 mayprovide the ability for the UI View 6208 to record sub-stateinformation, such as a current presentation mode, in the UI Model. Thisallows the GUI to resume operation in its prior state in the event of auser interface computer 6119 reset.

The UI Model 6206 may accept user-input data and requests, such as arequest to start a therapy, from the UI View 6208. Data integrity of anyinformation submitted via the UI View 6208 may be enhanced or ensured inseveral ways, such as by sending data submitted via the UI View 6208through the UI Model 6206 for verification. That is, while data may beedited locally in the UI View 6208, the accepted data may be transferredto the UI Model 6206 to be verified and recorded into database 6302and/or sent to the Therapy Applications 6203. Verification may comprise,for example, verifying that entered data is within an expected range.Any entered information may be then read back from the database 6302 bythe UI Model 6206, and sent to the UI View 6208 for display to the user.This process may be used to ensure that data stored in the database 6302is correct or as a user intended. Data integrity may also be enhanced byrequesting verification, by the user or another party, of entered data.

As shown in FIG. 63 , direct authority to control the TherapyApplications 6203 in response to inputs received from the userinterface, and thereby affect machine state, may be limited to the UIModel/UI Controller 6303 running on the automation computer 6106. Inaddition, direct authority to change information in the database 6302may be limited to the UI Model/UI Controller 6303. In this case, the UIView 6208 and Auxiliary Applications 6301 may have read access to thedatabase for actions such a viewing a log, but may not have write accessto the database 6302, at least under most circumstances. In this way,actions that could have safety-critical implications may be isolated onthe automation computer 6106. Of course, in some situations, it may bedesirable to allow the UI View 6208 and Auxiliary Applications 6301 tohave limited write access to the database 6302, such as to write to aparticular portion of the database or to write non safety-related datato the database. In addition, in some embodiments, it may be desirableto allow the UI View 6208 to directly control aspects of the TherapyApplications 6203.

The Auxiliary Applications 6301, discussed above, may comprise log ordocumentation viewers, for example. These Applications 6301 may run onthe user interface computer 6119 and operate in their own process space.However, to enable the UI View 6208 to control these applications, theAuxiliary Applications 6301 may be clients of the UI View 6208. Thisallows the UI View 6208 to communicate with the applications in astandard manner and allows the UI View to monitor these processes.

The UI Controller 6204 may comprise a table-based hierarchical statemachine (HSM) that determines the state of the screens displayed by theUI View 6208 based on data polled from the Therapy Applications 6203,local timeouts, and command requests or data received from the UI View6208. As represented in FIG. 63 , the UI Controller 6204 may access andwrite data to the database 6302 as required. The state of the HSM in theUI Controller 6204 may determine the major state of the set of screensdisplayed by the UI View 6208.

An exemplary HSM that may be used by the UI Controller 6204 to determinethe state of the screens displayed by the UI View 6208 is schematicallyshown in FIG. 64 . As shown, the HSM 6400 determines the state of“normal” (i.e., non-alarm) level interactions 6401, including thecurrent functional state 6402 of the user interface and the current menustate 6403. The HSM 6400 shown in FIG. 64 is merely exemplary, and maybe implemented in a much more detailed manner. For example, the statedesignated “Prepare” 6404 may involve several states relating topreparation for treatment, including a “gather supplies” state, an“install chemicals” state, the entering of patient information, and avalidation screen. The validation screen gives the user the opportunityto return to any of the prior data entry screens so that inaccurateinformation can be corrected before the “Prepare” state is exited. TheHSM 6400 also shows an alarm state 6405 that may be triggered. The alarmstate is described in connection with FIG. 65 .

The UI View 6208 may have the ability to take over the screen display atany time in order to display alarms. An alarm condition may be triggeredin certain circumstances to notify a user or other individual of anabnormal or otherwise noteworthy condition, such as a fluid leak, anocclusion, or an out-of-range temperature. When an alarm conditionoccurs, the state of the UI Controller 6204 may change. As shown in FIG.65 , when the UI View 6208 polls the UI Model 6206 for the currentstate, the UI View will change the display view from a normal state 6501to an alarm state 6502 displaying alarm information 6503. When in analarm condition, the UI View 6208 may prevent other information fromblocking the display of the alarm. However, even during an alarmcondition, the display may be configured such that a user may activate a“help” button to access additional information. In this case, helpinformation 6504 may be laid out so that the help information coversonly a portion of the view. Safety-critical logic of the alarm display,such as silencing logic, may be controlled in the automation computer6106. For example, if a user would like an alarm to be silenced, anindication of the silencing request may be relayed back to the UIModel/UI Controller 6303, which can allow the audible alert to besilenced temporarily. In each of the alarm state and the normal state,alternate views 6505 and 6506, respectively, may be possible.

As explained above, when an alarm occurs, the normal UI View state isterminated so that the alarm state information can be displayed. Anylocal screen selection and/or editing data may be lost when the screenis changed. Since it may be desirable to preserve this information, theUI View 6208 may request that the UI Model/UI Controller 6303 storesinformation related to the screen displayed just prior to the alarmcondition (i.e., the screen related to the normal state). At theconclusion of the alarm, if the normal state has not changed, the UIView 6208 may retrieve the stored information and restore the screendisplay. As an additional benefit, this feature may be used to restorethe prior view in the event that the user interface computer 6119 isinadvertently reset.

Therapy behavior is modeled and implemented as hierarchical statemachines that define each activity and user interaction as discretestates. As shown in FIG. 66 , the Therapy Layer 6601 is between the UserInterface Model Layer 6602 and the Machine Layer 6603. The Therapy Layerboth generates data and uses data stored in the Database 6604, whichalso shares data with the User Interface Model Layer.

The Therapy Layer 6601 controls the state of the system as a whole, anddictates available user interface interactions. The Therapy Layer 6601is polled for state/status information by the User Interface Model Layer6602. The Therapy Layer 6601 accepts user state change requests andchanges to the Therapy Settings 6605 from the therapy settings 6606 onthe User Interface Model Layer 6602. The Therapy Layer 6601 directs theMachine Layer 6603 in controlling the fluid path flows by issuingcommands 6607 from Therapy Control and Applets 6608. The Therapy Layer6601 polls status information 6609 from the Machine Layer 6603 todetermine the state of processes.

Information read from and written to the Database 6604 may includeComponent Status 6610, Component History 6611, User Parameters 6612,Therapy Limits 6613, Therapy Settings 6614, and Therapy History 6615.For example, replaceable component information may be read from andupdated to the Database 6604, and required fluid use and disinfectinformation may be read from the Database 6604. The Therapy Layer 6601periodically writes Therapy Status 6616 information to the Database 6604for logging purposes and to facilitate recovery in the event of atemporary power loss. The Therapy Layer 6601 also updates the Database6604 with Component Status information 6617.

All inter-processor communications may be performed via server-definedclient application programming interfaces (APIs) as remote processcalls. The Therapy Layer 6601 may block when making Machine Layer andDatabase interface calls via their respective Client APIs. However,during critical functions, such as while performing patient therapy, theTherapy Layer generally will not perform any blocking database accesses.Generally, only non-critical updates to the database are performed usingasynchronous (one-way) writes.

The User Interface Model Layer 6602 may block when making Therapy Layercalls via the Therapy Client API. The processes of the Therapy Layer maybe considered higher-priority than those of its clients, such as theUser Interface Model Layer 6602.

The system may handle exception conditions or errors generally in one ofat least three ways. A system error detected in the software orassociated with the CPU (such as, for example, a memory failure) callthe reliability of the system into question, and trigger a failsafestate. A therapy error or condition may occur if a therapy variableapproaches or exceeds permissible bounds. At least an alert or alarm (anevent requiring user action) are triggered, and the condition is logged.Finally, system operation conditions can be triggered and logged to thedatabase for later retrieval and analysis if problems are reported by anoperator or service technician.

Generally, the Machine Layer 6603 will not change state unlessexplicitly requested by the Therapy Layer 6601. Thus, the Machine Layer6603 generally should not generate an error in response to a changerequested by the Therapy Layer 6601, assuming that the Therapy Layer6601 makes change requests that are valid for the current operatingstate. As a result, Machine Layer 6603 command errors may not betolerated. An exception is when a “Pause-Freeze-Stop” button is actedupon directly by the Machine Layer 6603 prior to Therapy Layer 6601interaction. In this case, the Machine Layer 6603 will ignore anysubsequent Therapy Layer 6601 commands until the Therapy Layer confirmsthe “Pause-Stop-Freeze” action.

Exception cases (e.g. in the event of a blood leak, or air in a line)and orthogonal states may be prioritized such that the state presentedto the external User Interface Model Layer 6602 can be resolved to aunique current state. If multiple orthogonals attempt to set the userinterface state, generally only the last orthogonal processed will bepresented. Unexpected exceptions may be handled by commanding a FailSafe state.

As explained above, the Therapy Layer 6601 software is a state-basedcontrol layer between the Machine Layer 6603, and the User InterfaceModel Layer 6602. The interface and access methodology that the TherapyLayer 6601 presents to the User Interface Model Layer 6602 are discussedbelow.

The Therapy Layer 6601 is a state-based layer that receives commandrequests from the User Interface Model Layer 6602. Some commands arevalid from any state. Others are state specific, and the Therapy Layer6601 will decide if the current command request will be acted upon ornot. If the current state is not valid for the command request, therequest from the User Interface Model Layer 6602 will be rejected and anappropriate reason for the rejection will be returned to the client. Inthis way, safety-critical operations will be protected from commandsthat are inappropriate in the current state. Only safe and validatedoperator command activities may be processed. The Therapy Layer 6601interface to the User Interface Model Layer 6602 may be a server, andthe User Interface Model Layer 6602 may access it as a client processusing standard IPC client/server connection methods.

Synchronization between the Therapy Layer 6601 and the User InterfaceModel Layer 6602 may be based on two state-based enumerated types: the“Master State” and the “Sub-State.” The Master State indicates thecurrently active Therapy Layer 6601 state machine. The Sub-Stateprovides a unique state indication that can identify all of the alarms,user interaction, or the therapy sub-states that have duration. Thesestate variables are updated in Therapy Status messages. This allows theTherapy Layer 6601 to verify what the active user operation is in aresponse to and provides the context to commands like “continue.”

Turning now to the Machine Layer 6603 shown in FIG. 66 , an exemplaryimplementation of the Machine Layer is shown in FIG. 67 . The machinesoftware is a layer of abstraction that provides the ability toimplement a specific set of operations. These operations include primingthe system, performing dialysis, disinfecting, draining and selftesting. The machine software operates specific valves, runs pumps,controls flow paths and takes measurements. During the operations of theMachine Layer, status information can be requested at any time withoutinterfering with operations.

With reference to FIG. 67 , one state of the Machine Layer State Machine6701 is the Primed With Water state 6702. This state is reached bysending the primeWater command 6703 and allowing the operation Primewith Water 6704 to complete. In the Primed With Water state 6702, thefluid paths are filled with reverse osmosis (RO) water and purged ofair. In addition, this state is used to rinse, disinfect and performvarious tests including flow tests and hydraulic integrity tests.

The Air Filled state 6705 is used to run the dialyzer and ultra filterintegrity tests and for replacing components. In this state, the systemmay have had as much of the fluids removed as practically possible.

Dialysis treatment is performed in the Treatment state 6706. This stateis entered by sending a command 6707 to set up the parameters of thedialyzer and the ultrafilter. For example, the setupDialyzeParamscommand 6707 may communicate the parameters of the installed disposablefilters and the size of the needle/catheter. The initial state of theTreatment state 6706 is the Setup Dialyze Parameters state 6708.

The command issued by the Setup Dialyze Parameters state 6708 depends onthe dialysate source. If the source is bagged dialysate, theprimeDialysate command 6711 is issued and the process proceeds directlyto Prime with Dialysate 6709. If the system is making dialysate from abicarbonate cartridge and acid, the connections have to be verified. Inthis case, the CheckChem command 6712 is issued and the process proceedsto the Check Chem Connections state 6710. A dry test can be used toverify that an empty chemical container is connected. A wet test can beused to verify that a primed chemical container is connected bydetecting the presence of no or minimal air in the container. Positiveor negative pressure can be applied to the chemical container to detectthe presence of loose connections or leaks. Conversely, a “CheckBypass”test can be performed to verify that the bypass connector is in place.Positive or negative pressure in the flow path can be measured todetermine whether the chemical concentrate containers and tubing or thebypass connector are present. Positive or negative pressure can also beapplied to determine the presence of any leaks associated with theconnector. When this state is complete, the primeDialysate command 6711is issued and the process proceeds to Prime with Dialysate 6709.

When using bagged dialysate, the priming process begins immediately.When making dialysate from reverse osmosis water, the system shouldprime the bicarbonate cartridge and cause the conductivity of thedialysate to stabilize at the requested level. Then, the dialysate tankshould be filled to a minimum level. The system primes itself by runningthe pumps in the dialysate circuit forward and backward to drive air outof the cassette. The conductivity sensors can be checked during primingto ensure that their readings remain consistent. The system finishespriming by driving dialysate through the dialyzer and into the bloodloop. Priming here can also involve forward and backward flow to helppurge any air from the blood loop. The arterial and venous lines canalso be isolated at times to purge the air more efficiently. Priming ofthe blood loop also serves to meet the minimum rinse volume required forthe dialyzer before treatment. When this process is complete, thepatient can be connected.

Before the start of a treatment, a Set Fluid Production Parameterscommand may be sent to the machine layer 6701. This command communicatesthe necessary information to either make dialysate or use pre-madedialysate. For example, the following dialysate information may beprovided: bicarbonate cartridge priming volume (ml), bicarbonatevolumetric ratio (mg/ml), target dialysate conductivity (mS/cm @ 25° C.)after addition of acid and salt (final dialysate composition), and acidvolumetric mixture (ml acid/ml water). The following dialysate sourceinformation may be provided: reverse osmosis (RO) water or premadedialysate (RO/Bagged), and pre-made dialysate volume (ml).

The Pneumatic Integrity Test operation 6715 verifies the pneumaticdevices in the system. This operation may check for leaks and verifysensors. This operation may comprise the following individual tests,which may be run individually or all in sequence: a cassette leak test,a pressure pump test, a meter pump test, and a dialysate tank leak test.The cassette leak test tests for air leaks in the valve manifold, thepressure pump chambers and the plumbing. The fluid valves are closed onall pressure pumps, and then positive varivalves are opened. Next, thecompressors are activated and the pneumatics are pressurized. After atarget pressure is reached, the compressors are turned off and thesystem pressures are monitored, e.g., for 10 seconds. At the end of thattime, if the pressures are above a threshold, the test passes. Then thetest is repeated with negative varivalves. The meter pump test chargesFMS chambers with positive pressure, and verifies that the FMS chambersreach the pressure. The positive pressure valves are closed, and thesystem verifies that they do not leak more than the test threshold. Theprocess is repeated with negative pressure. In some cases, the pressuredecay rate is used to determine whether a leak test passes.

The Hydraulic Integrity Test operation 6716 verifies the fluid valves inthe system. In this test, pump chambers are filled with water and thechamber is driven, and valve leaks are detected by measuring thepressure drop in the pump chamber. The operation is divided up into setsof valves based on which pressure pump drives fluid through the valve.

The Ultrafilter Integrity Test operation 6717 is a pressure test of theultrafilter membrane to check for leakage. Air pressure is applied tothe inlet side of the ultrafilter. Air pressure is maintained, since airgenerally will not pass through a wet intact filter. This test isperformed in the “Air Filled” state, and verifies the ultrafilter bypressurizing the outer dialysate side and measuring the pressure dropover time.

The BTS/Dialyzer Integrity Test operation 6718 is a pressure test of theblood loop including the dialyzer. In this test, the blood loop ispressurized and the pressure is monitored over time. If the measuredpressure drop is less than the input decay threshold, the test passes.As the blood tubing, pump and dialyzer are replaced as a unit, this testneed not determine where the leak is.

The Impedance-Based Clearance Test operation 6719 verifies that theblood path through the dialyzer has low enough resistance to provideefficient dialysis therapy. Before starting the impedance test, thesystem is primed with water. During the test, flow is forced across thedialyzer. As water flows across the dialyzer, the pumping pressures willbe monitored, which provides a measure of the dialyzer impedance.Alternatively, a constant pressure can be applied, and the time takenfor a fixed volume to cross the filter membrane can be measured. Thedialysate circuit is set to provide a constant low impedance destinationof the fluid being pushed through the membrane. If the dialyzerimpedance is too high, a failure will be reported and the dialyzer willneed to be replaced. An Ultrafilter Flow Test operation 6724 may be alsoperformed to ensure that the ultrafilter impedance is low enough tosupport the flow rate required for therapy. This test has the benefit ofensuring that the result of the integrity test will be valid.

The Empty Dialysate Tank state 6720 may stop fluid production and runthe dialysate pump at the fastest reasonable rate to pump the contentsof the dialysate tank to drain until some amount (e.g., 3000 ml) hasbeen transferred, or air is detected in the drain. The Deprime operation6721 is used to purge the system of fluid, filling the blood tube setand the dialysate circuit outside of the ultrafilter with air. Thiscondition is used to perform pressure-decay tests to verify theintegrity of the dialyzer and ultrafilter, as well as to change thefluid components and to prepare the unit for transport. The innerdialysate circuit generally cannot be deprimed because it may not bepossible to pump air through an intact dialyzer or ultrafilter, andthere may be no air vent in the inner circuit.

The Prime with Water operation 6722 fills the system with water andpurges the air. It may fill the system in stages, starting with thefluid production section, and moving to the outer dialysate, innerdialysate, and then the blood loop. The bicarbonate cartridge and acidbag should be removed, and a bypass connector should be in place beforethis operation is performed. According to one exemplary implementation,the bypass connector comprises three connection points respectivelycorresponding to a bicarbonate charge line, an acid flow line and abicarbonate return line of the mixing circuit 25. The bypass connectorhas three parallel prongs respectively corresponding to the threeconnection points. Channels in the prongs of the bypass connectorterminate within a common chamber within the bypass connector. Thus,during a disinfect procedure, the bicarbonate charge line, acid flowline and bicarbonate return line are all interconnected, permittingdisinfection of each of these flow lines during the disinfect procedure.An exemplary embodiment of such a bypass connector is the “disinfectconnector” described in U.S. patent application Ser. No. 12/199,055filed on Aug. 27, 2008 and issued as U.S. Pat. No. 8,393,690.

The Disinfect/Rinse state 6723 is used to run reverse osmosis waterthrough all fluid paths at a specified temperature. Before thisoperation, the system should be in the “Primed With Water” state 6725.Disinfection occurs when this operation is performed at an elevatedtemperature. The tank is filled with reverse osmosis (“RO”) water at thestart of the operation. The water in the dialysate tank is recirculatedfrom the Dialysate Circuit disinfect path through all Fluid Productionfluid paths and blood tubing set paths, and back into the dialysatetank. As recirculated water is lost (sent to drain), reverse osmosiswater may be added to maintain a minimum level in the dialysate tank.Alternatively, in a preferred embodiment, no further water is introducedin order to avoid the possibility of contamination. The chemicalcartridge is not attached during this operation.

The Prime with Dialysate operation 6709, described above, is used toflush dialysate through all fluid paths and remove any air or water inthe system. This operation must be completed before the system can moveon to the Patient Connected state 6713. This operation activates thefluid production sub-system, which is responsible for mixing the ROwater with the chemicals, and for maintaining the dialysate tank level.If the tank is less than 75% full, priming may be delayed until thatlevel is reached. The tank level is preferably maintained at more than1.1 liters; otherwise, a signal may be generated to stop therapy. Thisamount allows for a sufficient rinseback volume and a sufficiently largeaveraging volume needed for mixing control accuracy. During prime, theair-in-line sensors, the blood-leak sensor and the safety system aretested.

In the Patient Connected state 6713, a dialysis treatment can beperformed. Prior to issuing the RinseDialysate command 6714, the bloodtubes are returned to drain connections. For safety purposes, while inthe Patient Connected state 6713, the dialysate temperature may beconstrained, and the dialysate conductivity and flow rates may bemonitored.

The Prime With Blood operation 6726 removes dialysate from the bloodcircuit and replaces it with patient blood. Dialysate is pulled acrossthe dialyzer membrane into the dialyze circuit and is discarded todrain. Blood is pulled into the blood circuit from the patient toreplace the dialysate pulled across the membrane. Thus most of thepriming fluid occupying the BTS need not be administered to the patientat the start of dialysis. Optionally, the patient can choose to beadministered the priming fluid by canceling this operation. This may bedesirable, for example, if the patient is in need of additional fluid atthe start of dialysis. This operation transitions the machine softwareinto the Patient Connected state 6713, activating safety constraintssuch as temperature limiting.

The Heparin Bolus operation 6727 delivers a bolus of heparin beforetreatment without requiring patient interaction. Before normal dialysisoperation, and to minimize the amount of fluid administered to thepatient, the bolus can be delivered down the arterial line, which is ashorter route to the patient's vascular access. In the event of thedetection or presence of an air-in-line condition, the heparin bolus canoptionally be delivered down the venous line, which incorporatesair-trapping mechanisms or devices.

The Dialyze operation 6728 is used to administer dialysis treatment tothe patient. The rate of the blood circuit and the dialysate circuit maybe specified independently. This operation can have a time limit or beterminated with a stop command. By way of example, the followingparameters may be specified: the temperature at which the dialysateflowing through the system is heated and maintained, the rate at whichdialysate is circulated through the blood circuit, the rate at whichbasal or maintenance heparin is added to the blood circuit, the rate atwhich dialysate is circulated through the dialysate circuit, and therate at which dialysate is pumped through the ultrafiltration pump,among other parameters. During dialysis, the ultrafilter is periodically‘burped’ to remove any gas that has accumulated within it duringtreatment. This can be accomplished by opening the pathway from the topof the ultrafilter to drain while closing the pathway fro the top of theultrafilter to the dialysate circuit. Any air trapped in the top of thedialyzer can then be flushed to drain. After two or more pump strokes todivert the air and fluid to drain, the valves are reset and dialysisoperations can continue.

The Power Loss Recovery 6733 command may be sent to tell the machinesoftware that there was loss of power while it was in the PatientConnected state 6713. This forces the machine software into a PatientDisconnected state so that the dialysis machine can recover properly andprepare itself for the next treatment (e.g., Recycle Preparation).

The Solution Infusion operation 6729 delivers dialysate into thepatient. Dialysate is pushed across the dialyzer by the outer dialysatepump and delivered to the patient by the blood pump. This command causesthe system to prepare for the infusion by stopping dialyzing, freezingthe inner pump, and filling the outer pump with dialysate to deliver tothe patient. After receiving this command, the machine software expectsone of the following commands: Solution Infusion Confirm (proceed withsolution infusion), Dialyze (do not perform solution infusion, resumedialyzing instead), or StopCmd (return the system to an idle state).Preferably, the blood pump continues to run during solution infusion.

A Backflush operation can be programmed during dialysis to periodicallyflush dialysate backwards across the dialyzer membranes in order to helpprevent clotting of the membranes. The Rinse Back operation 6730 pushesdialysate into the patient to return their blood in preparation fordisconnection. Dialysate is pushed across the dialyzer by the outerdialysate pump and delivered to the patient. This is automated for bothvenous and arterial paths.

The Check Bypass operation 6731 checks for the presence of the bypassconnector for the acid container and the bicarbonate cartridge orcontainer. In a preferred embodiment, the operation causes a vacuum topull on the bypass connector to detect leaks. The Drain Chemicalsoperation 6732 empties the contents of the chemical containers to thedrain. In a preferred embodiment, the contents of the chemicalcontainers are discarded after each treatment, making cleanup easier forthe patient and discouraging potential problems in trying to reusechemicals.

A CheckDoors operation verifies that the doors of the hemodialysismachine are closed, helping to ensure that the patient is disconnected.A CheckDCA operation can then verify that the patient has plugged thevascular access connectors of the blood tubing set back into the DCA/DCVports of the machine for rinsing and disinfecting after a treatmentsession.

In addition, a Clean Blood Path operation may be performed to push thecontents of the dialysate tank through the blood circuit and out thedrain. Rinsing is used to flush residual blood from the blood circuitand dialyzer after the dialysis treatment. In an embodiment, air isintroduced into the fluid to enhance the mechanical action of looseningdebris from the dialyzer and tubing components. During this operation,fluid production may deliver water, which will dilute the dialysate inthe tank.

A Recirculate operation may be used to maintain the temperature anddialysate freshness in the system after it has been primed when thepatient is not yet connected. This is accomplished by running dialysatethrough the heater, ultrafilter into the inner pump, and passing itthrough the dialyzer, while also running the blood pump. A small amountof the dialysate can be constantly sent to drain.

The Machine Layer 6701 may also respond to stop, freeze, resume, andshut down commands. The stop command terminates the operation beingperformed by machine. When the stop command is issued, the current pumpcycle is completed, then the valves are all closed. Because the strokeis completed, all fluid accounting will be accurate. After all valvesare closed, the state machine returns to the “idle” condition where itwaits for the next command. This command does not affect thegetStatusCmd, setupDialyzeParams or setupFluidParams commands becausethey do not start operations.

The freeze command causes the system to close all valves on its currentcycle. This includes the fluid production valves. The heater is turnedoff to prevent overheating of the fluid within it. Fluid volumeaccounting will be correct if the resume command is issued after thefreeze command. If the freeze command is followed by a command to enteran operation other than the one that was frozen, fluid volumes areassigned to the new operation regardless of the fact that there may bepartial fluid delivery in the original state. State history of thecurrent operation is retained so the “resume” command can be used tocontinue the operation. The resume command causes the machine tocontinue processing the command that was frozen. The shut down commandis used to terminate the machine software process.

The Therapy Applications 6203 shown and described in connection withFIGS. 62 and 63 run state machines that implement therapies implementedby the Machine Controller and I/O Server Process. The state machines mayperform such functions as treatment preparation, patient connection,dialysis, solution infusion, patient disconnect, recycle preparation,disinfect, rinse, and disposable replacement. The Therapy Applications6203 also comprise a master control module responsible for sequencingthe activity of all other therapy applications that prepare for anddeliver daily treatment.

Referring to FIGS. 62 and 63 , the Therapy Applications 6203 provide aninterface that allows the UI Model 6206 to start, stop and configuretherapies, as well as report therapy status. The Therapy Applications6203 also interface with the Machine Controller. In particular, theTherapy Applications 6203 issue commands to and request status from theMachine Controller in order to implement the therapy operations. Inorder to access patient, therapy and machine information, the TherapyApplications 6203 interface with the database 6302. It also uses thisinterface to store treatment status information.

Described below are individual applications of the Therapy Applications6203. These applications are (1) Recycle Preparation, (2) Clean BloodPath, (3) Disinfect, (4) Rinse Endotoxins, (5) Treatment Preparation,(6) Patient Connect, (7) Dialyze, (8) Solution Infusion, (9) Rinseback,(10) Take Samples, (11) Replace Components, and (12) Install Chemicals.

(1) Recycle Preparation

FIG. 68 shows an exemplary implementation of the Recycle Preparationapplication. The Recycle Preparation application prepares the system forrecycling. Prior to initiating recycling, the system confirms that thedoors are closed. This will allow the system to clean and disinfectsuccessfully, but also ensures that the patient has not inadvertentlyfailed to disconnect.

Next, the system prompts the user to remove and discard the chemicalconcentrate cartridge. The system first drains any remaining chemicalsto minimize any spillage upon removal. The user may elect to bypass thisdraining step if they wish to remove their cartridge immediately. Oncethe cartridge is removed and discarded, the user prepares the system forrecycling by installing the chemical bypass connector.

During chemical cartridge drain and removal, the system simultaneouslyperforms pressure tests to ensure that the operator has connected theblood tubing set (BTS) properly, including installing a vial on theheparin connector. In this way, the operator can be notified of andcorrect any problems while they are present. Then, the system cansuccessfully navigate through the remainder of recycling unattended.Testing is achieved by sequentially pressurizing the various sections ofthe BTS to ensure there are no kinks, clamps closed, or clots. BTSintegrity can also be checked by pressurizing the entire BTS anddialyzer with air after the dialyzer has been wet, and monitoring for athreshold pressure decay value that would indicate a leak in the bloodtubing, blood tubing connections, dialyzer or dialyzer connections. Thedisinfection ports are also checked to confirm that the venous andarterial lines are securely locked into their ports. If any of thesetests fail, the user may be notified of the specific failure andinstructed on how to correct it. The tests are repeated until all havepassed.

If the dialyzer and blood tubing set have reached the treatment ordisinfection usage limits or the operator chooses to replace them, thenthey may be replaced prior to recycling. If the ultrafilter has exceededthe ultrafilter transmembrane pressure (TMP) or impedance test limit,reached its disinfection usage limit, or the operator chooses to replaceit, then the ultrafilter may be replaced prior to recycling. To replacethese components, the user may invoke the Replace Components applicationdescribed in connection with FIG. 78 .

With reference to FIG. 68 , Recycle Preparation application 6801 isshown. The Monitor state 6802 monitors for a Pause request 6803 or adialysate leak 6804. Further during this state 6802, the system willconfirm that the doors are closed. The fact that the doors are closedimplies that the patient is not currently connected to the machine. Thischeck will be performed in the Checking Doors state 6805. If the doorsare closed, the process proceeds to the Post Treatment Data Entry state6806.

The Post Treatment Data Entry state 6806 may prompt the patient/operatorto enter miscellaneous post treatment data. If system indicates that pretreatment data was entered, the system will prompt the operator/patientto enter the post treatment data. The following post treatment data maybe requested: Post Treatment Weight, Blood Pressure, and Pulse Rate. Theinformation from these entries may be included in a systems log oftreatment report information. In addition, the system will not requirethis information to be entered in order to continue on with therecycling process. If the system indicates that pre treatment data wasnot entered, the system will not prompt the operator/patient to enterthe post treatment data.

The Check Source And Drain state 6807 confirms that the inlet watersource and drain are properly connected. This ensures that the systemcan successfully perform recycling. The Check Source And Drain Recoverystate 6808 provides the operator with information pertaining to asource/drain failure detected as well and required corrective actions.For example, the user may be notified that the inlet water source ordrain is not installed properly and may be instructed on how to correctthe problem.

The Chemical Concentrate Removal & Check BTS state 6809 will run twooperations concurrently. Completion of both operations will allow thesystem to continue on with the recycling operations. The operations thattake place during this state are: disposal and removal of the chemicalconcentrates and checking the BTS connections. The BTS and Dialyzerreplacement is also evaluated at this time. In the first operation, theChecking Chemical Concentration Presence state 6810 detects whetherchemicals are present or not to determine the next step. In particular,through the use of an air integrity test, the system will be able todetect the presence of the chemical concentrate container. In theChemical Drain state 6811, the system will perform the necessaryoperations to drain any residual chemical concentrates from thecontainers. The purpose is to make removal and disposal of thecontainers cleaner and easier, producing as little waste as possible.The user may be prompted that they can choose to bypass draining. TheRemoval of Chemical Concentrates state 6812 provides instructions to theuser to remove the chemical concentrates and close the chemical bypassdoors, and may provide instructions. Included in the instructions may behow to configure the machine so that it will be able to effectivelydisinfect the chemical concentrate ports. The Wait for Check BTS state6813 is an end point for the Chemical Disposal and Removal operations.The system will remain in this state until other concurrently performedoperations are complete.

Turning to the second operation that is run by the Chemical ConcentrateRemoval & Check BTS state 6809, during the Check BTS state 6814 thesystem evaluates whether BTS and Dialyzer replacement is required. Anoption may also be displayed allowing the operator to choose dialyzerand BTS replacement. This option may include data entry as to theclotting status of the dialyzer, and may remain available to the useruntil the Chemical Concentrate Removal & Check BTS state 6809 iscomplete. If no replacement of the BTS and Dialyzer is required orrequested, the system ensures that the BTS is properly connected forrecycling and then recirculates the BTS fluid to prevent clotting. TheBTS Connection Test 6815 confirms that the BTS has been connectedproperly for recycling. This may include ensuring that the patientconnectors have been properly installed into their disinfection ports,that the clamps have been opened and the BTS is not kinked, and that theBTS is properly installed in the air detectors and occluders. TheConnection Recovery state 6816 provides the user with information thatpertains to the failure detected, as well as corrective actions that arerequired. For example, the user may be notified that the BTS is notinstalled properly, and indicate the specific problem. The notificationmay include corrective actions that should be performed based upon afailure code from the BTS Connection test 6815. A DC Connection test maybe performed to verify that the patient has plugged the vascular accessconnectors of the blood tubing set back into the DCA/DCV ports of themachine for rinsing and disinfecting after a treatment session. AHeparin Vial Connection test may also be performed to verify that a vialis attached to the heparin/medication infusion spike on the blood pumpcassette. This ensures that disinfection fluid can enter and exit thevial and clean the vial spike and heparin fluid path in the process.

The Recirculate BTS Fluid state 6817 will start recirculating the fluidin the BTS to prevent the residual patient blood from becoming stagnantand developing clots. The system may be configured such that thisprocess can only be performed once the system has detected that the BTSconnections are properly inserted into the disinfection ports. The Waitfor Chemical Concentrate Removal state 6818 acts as a wait state thatwill allow the other operations that are concurrently taking place tocomplete. Once the system indicates that chemical concentrate removal iscomplete, the system will continue.

Regardless of which components are being replaced, the Check ComponentReplacement state 6819 may act as a transition point for the componentreplacements. It also evaluates whether ultrafilter replacement isrequired. If the ultrafilter has exceeded its TMP test limit or reachedits disinfection usage limit, then ultrafilter replacement may berequired. If BTS and dialyzer replacement was previously determined tobe required or was requested by the user, then the BTS and dialyzershould be replaced. If any replacement is required, this data istransferred to the Pause state 6820 where Replace Components 6821executes the activity. Once the replacement process has been completedby the system and the operator, the Recycle Preparation application willresume.

The Final Door Check state 6822 will perform a final check of the doorsto confirm that the doors are still closed. This is intended to preventany unnecessary alarms that might prevent the machine from recycling.The Doors Open Recovery state 6823 notifies the patient the doors areopen, and prompts the user to close the door.

The Pause state 6820 will halt operation and may allow the patient tochoose to perform additional activities. The Stop for Pause state 6824halts all machine operations. For example, the state may stop all flows.The Pause Menu state 6825 allows the patient to choose to performadditional activities, and may display the following options: ReplaceComponents 6821, Shutdown 6826, Power Standby 6827, and Resume RecyclingPrep 6828.

The Dialysate Leak Alarm state 6829 will stop operation and notify theuser that a dialysate leak has been detected. The Leak Resolution state6830 waits for the user to clear the leak, and for an indication fromthe user of the same.

(2) Clean Blood Path

Next, a method may be performed to clean blood and dialysate frompathways prior to disinfection. Residual blood and dialysate, left overfrom treatment, is rinsed from the dialysis unit prior to performingdisinfection. It is desirable to remove these substances because thedisinfect process makes subsequent removal more difficult. Further, isdesirable to remove residual blood and dialysate, as they are sources ofbacteria. Special care may be taken to clean the dialyzer effectively sothat its performance degrades as little as possible over multiplereuses.

Cleaning the blood and dialysate pathways may be accomplished byflushing a certain amount of fluid through those pathways and directingthat fluid to a drain. Cleaning the blood pathways may take more effortand require more thoroughness than cleaning the dialysate pathways dueto the blood and blood clots that reside in the blood pathways. Clotstypically attach themselves to the venous and arterial headers of thedialyzer, which may reduce dialyzer efficiency by obstructing itsfibers. Cleaning the arterial and venous headers may be difficultbecause their large volumes provide spaces of low flow where clots canmigrate. In order to remove these residual clots from the dialyzerheaders, it is desirable to first loosen or dislodge them. This may beaccomplished by pushing fluid both through the dialyzer and across it,while increasing or maximizing flow rates, thereby creating ormaximizing turbulence. Blood clots may also be loosened by moving fluidinside the BTS back and forth by controlling each blood pump chamberindividually. The inner dialysate pumps and the BTS drain are closed,and blood chamber 1 is made to deliver fluid as blood chamber 2 fills.Once both are idle, blood chamber 1 fills as blood chamber 2 delivers.This cycle may be repeated a number of times (e.g., approximately 20cycles). Air may also be injected into the BTS, and mixed with the waterto increase the mechanical action to loosen debris. In one embodiment,air is drawn through the heparin air filter into a blood pump chamber,and is then delivered to the BTS. The displaced fluid in the BTS may bedischarged to drain. The blood pump can then be run for a number ofcycles (e.g. 40 cycles) at a specified rate and direction (e.g., 500ml/min in a backwards direction).

FIGS. 69 a and 69 b show an exemplary implementation of the Clean BloodPath application. With reference to FIG. 69 a , Clean Blood Path 6901 isthe top level state which coordinates the actions of the overallprocess. This state runs concurrently with the data handling elements ofthe state machine. During this state, residual blood and dialysate, leftover from treatment, are rinsed from the machine. Updates to data ofinterest to the application will be processed by the data handlingelements of the state machine. The Pause and Dialysate Leak Monitorstate 6902 watches for certain failures and pause requests. Dialysateleak monitoring may be requested. The Alarm Monitor state 6903 watchesfor certain failures. Complete blood-side occlusion monitoring isrequested, and inlet water monitoring is enabled. The Flush ArterialLine with Dialysate state 6904 takes a portion of the residual dialysateleft over from treatment and flushes it through the arterial line andout to a drain. Flushing blood out with physiological fluid, such asdialysate, prior to sending water to the blood tubing set (BTS) may bedone in order to minimize the hemolysis and foaming that occurs whenblood is exposed to water. When blood foams, it typically makes cleaningmore difficult. Similarly, the venous line may be flushed with dialysatein state 6919. The Empty Tank state 6905 removes any residual dialysatefrom the dialysate tank by sending it to a drain. The Prime FluidProduction state 6906 primes the fluid production module with water inpreparation for rinsing. The Prime Flowpath state 6907 primes the entireflowpath with water in preparation for rinsing. The Stop FluidProduction state 6908 primes the entire flow path with water inpreparation for rinsing, and stops fluid production.

The Rinse Pathways state 6909, shown in FIG. 69 b , rinses all fluidpathways in order to flush residual blood and dialysate out of thesystem. This state will also start fluid production. With reference toFIG. 69 b , the Recirculate state 6910 recirculates fluid in both theblood circuit and the dialysate circuit. The Blood CircuitDrain—Arterial state 6911 flushes fluid out through the arterial bloodcircuit line to a drain. The Blood Circuit Drain—Venous state 6912flushes fluid out through the venous blood circuit line to drain.Flushing blood out with physiological fluid such as dialysate prior tosending water to the BTS is done in order to minimize the hemolysis andfoaming that occurs when blood is exposed to water. The DialysateCircuit Drain state 6913 flushes fluid out to drain from the dialysatecircuit, while recirculating fluid in the blood tubing set. The FluidPrep Circuit Drain state 6914 flushes fluid out to drain from the fluidpreparation circuit, while reverse recirculating fluid in the bloodtubing set. The Recirculate UFTR state 6915 recirculates fluid throughthe ultrafilter flush port, while recirculating fluid in the bloodtubing set. The Dialysate Tank Upper Level state 6916 maintains thedialysate tank at a full level. Cycling the fluid level in the tank upand down acts to rinse the tank. The Dialysate Tank Lower Level state6917 maintains the dialysate tank at a near empty level.

Either at this stage or near the beginning Disinfect, the metering pump(e.g. heparin pump) on the blood pump cassette may be directed to emptythe medication (e.g. heparin) container. The medication may be replacedwith either dialysate or water, but preferably the container is filledwith air in preparation for the instillation and withdrawal ofdisinfection fluid during Disinfect. If the medication is heparin, anyresidual heparin remaining in the container or vial after a treatmentsession can be emptied into the BTS at this stage. Circulating theresidual heparin through the BTS during Clean Blood Path or Disinfectmay help to reduce clot formation and thus increase the efficiency ofthe cleaning process. Alternatively, the heparin may be discarded todrain.

Referring again to FIG. 69 a , the Stop Rinse state 6918 stops therinsing process. The Completion state 6920 finishes the application byemptying the dialysate tank. The Occlusion Recovery state 6921 handlesthe correction of any occlusions that have been detected by the system.The Occlusion Alarm state 6922 will stop Clean Blood Path 6901 andnotify the patient there is an occlusion. The Occlusion Resolution state6923 waits for the patient to clear the occlusion.

The Inlet Water Recovery state 6924 may handle the correction of anyinlet water occlusion that has been detected by the system. The InletWater Alarm state 6925 will stop Clean Blood Path 6901 and notify thepatient there is a problem with the incoming water. The Fill DialysateTank state 6926 attempts to fill the dialysate tank. The Pause state6927 will halt operation. Additionally, the patient can choose toperform additional activities. The Stop for Pause state 6928 will haltall machine operation. The Pause Menu state 6929 allows the patient tochoose to perform additional activities. The following options may bedisplayed: Take Samples (RO Sample) 6930, Replace Component 6931, PowerStandby 6932, Shutdown 6933 and Continue Operation 6934.

The Dialysate Leak Alarm state 6935 will stop operation and notify thepatient a dialysate leak has been detected. The Leak Resolution state6936 waits for the patient to clear the leak, and may allow the continuebutton to be displayed on the GUI.

(3) Disinfect

Following the recycle preparation and the cleaning of the blood path,the Disinfection Application may implement the disinfection of fluidpathways. Disinfection is performed to provide fluid that is ofinfusible quality. To achieve this goal, the disinfection process maykill all vegetative bacterial cells, fungi, and all small or non-lipidviruses. Because the machine is generally dedicated to one patient, itis not imperative that the disinfection process eliminate viralcontamination. Switching the machine between patients may require stepsbeyond this process. Disinfection may be achieved by bringing all fluidpathways to a certain temperature and holding that temperature for aminimum amount of time. For example, water circulated through thedialyzer, blood treatment set, ultrafilter, and dialysate set may beheated to a temperature of 85° C., ±5° C. for approximately one hour.Hot water pasteurization may be suitable for high-level disinfection.Exemplary conditions for hot water pasteurization may comprise atemperature of approximately 68° C. for a minimum of about 30 minutes.The Disinfect state is able to monitor the temperature at various pointsin the system and delays disinfection until the sensors are at leastabout 1° C. above the target temperature. The state monitors thetemperature at various points and takes action to increase fluid heatingif any sensor falls below the target temperature, for example, for morethan 10 consecutive seconds.

FIGS. 70 a and 70 b show an exemplary implementation of the Disinfectapplication. FIG. 70 a shows the Disinfect state 7001, which enables thedialysis unit to disinfect itself. The Data Handler Init state 7002handles reading data values from the database. The values may be in thefollowing tables: Instrument, Dialyzer Use and Reuse, Ultrafilter Useand Reuse, Blood Tubing Set Use and Reuse, Disinfection, Expirations,and Treatment Flow sheet. The Data Handler Update Complete state 7003handles updating data values in the Database once Disinfect has beencompleted. During the Idle state 7004, the history of the Disinfectstate 7001 is cleared upon performance of Clear Disinfect History 7005.Start Disinfect 7006 transitions the process to the Active state 7007.The Active state 7007 watches for Disinfect Stop 7008. Disinfect Stop7008 transitions the process back to the Idle state 7004. The Monitorstate 7009 watches for the doors of the dialysis unit being opened,occlusions, and requests to Pause 7011 dialysis unit operations. If theuser requests Pause 7011, the application proceeds to the Pause state7010.

In the Monitor state 7009, the Fill Tank state 7012 starts reverseosmosis (RO) water production and fills the tank prior to priming theflow path. The Prime Flow path state 7013 primes the entire flow pathwith water in preparation for disinfection. The Disinfect Flow pathstate 7014 oversees disinfection of the machine and determines when itis complete. It starts flows and recirculates fluid in both the bloodcircuit as well as the dialysate circuit. Disinfection may be deemedcomplete when all temperature sensors remain at least 1° C. above thetarget temperature for a selected number of consecutive minutes. Ofcourse, alternative parameters may be used to deem the disinfectioncomplete. When such a determination is made, the event DisinfectComplete 7015 is generated. The Warm Up state 7016 monitors thetemperature at various points and waits for portions of the dialysisunit to heat up. When all temperature sensors are at least 1° C. abovethe target temperature, the event Flowpath At Temp 7017 may be isgenerated. The Hold Temperature state 7018 monitors the temperature atvarious points and takes action if the monitored temperatures drop toolow. For example, the event Flowpath Below Temp 7019 may be generatedwhen the temperature at any sensor falls below the target temperaturefor more than 10 consecutive seconds. Other parameters may alternativelybe used. The Empty Tank state 7020 empties the dialysate tank. In thisway, the drain line receives a final round of disinfection. Further, anempty tank end condition allows for future applications to start with aknown tank level. The Done state 7021 is the completion state forDisinfect.

The Occlusion Stopping state 7022 stops all flows and notifies the userthat an occlusion has been detected. The Occlusion state 7023 waits forthe user to indicate that the obstruction has been cleared. Once theUser indicates that the problems have been corrected, the event User OK7024 is accepted. The Doors Open Stopping state 7034 stops all flows.The Doors Open state 7025 prompts the user to close the doors of thedialysis unit. Once the user indicates the doors have been closed, theevent User OK 7026 is accepted.

Referring now to FIG. 70 b , the pause behavior will be discussed. ThePause Wait for Stop state 7027 waits for all operations to stop. Whenthe machine is stopped, the event 7028 is generated. The Pause Wait ForUser Choice state 7029 prompts the user to choose the next step andwaits for the user to choose what they want to do. The patient will havethe following options: Take RO Sample 7030, Power Standby 7031, andShutdown 7032. The User Take RO Sample state 7030 waits while the usertakes an RO Sample, the Power Standby state 7031 waits for PowerStandby, and the Shutdown state 7032 waits for Shutdown. The user mayalso select a Resume operations option to generate a Resume Requestedevent 7033 (FIG. 70 a ).

(4) Rinse Endotoxins

Following disinfection of the fluid pathways, endotoxins and deadbiofilm may be rinsed from the pathways via the Rise EndotoxinsApplication. Endotoxins are part of the outer cell wall of bacteria andare released when bacteria are killed. Biofilm is a complex collectionof microorganisms that attach to available surfaces. While thedisinfection process kills viable biofilm bacteria, it may not removeall the biomass components, including endotoxins.

To remove dead biofilm and endotoxins, a certain amount of fluid isflushed throughout the flow path at a certain flow rate. Thisapplication is designed to rinse each tubing segment with at least threetimes the holding volume of that segment, although other implementationsare possible. According to one exemplary implementation, the deadbiofilm may be removed to achieve a Reynolds number of at least 100.According to another exemplary implementation, the Rinse Endotoxinsapplication may be designed to achieve a Reynolds number of 200 or more.

FIG. 71 shows an exemplary implementation of the Rinse Endotoxinsapplication. In the Rinse Endotoxins application 7101, the Prime WithWater state 7102 introduces fresh cool reverse osmosis water into thesystem that has just completed disinfect. Fluid Circuit Rinse 7103 isdesigned to rinse every fluid line of the system. The Recirculationstate 7104 flushes the Fluid Production, Fluid Preparation,Recirculator, Dialyzer, Blood Circuit and access lines with reverseosmosis water. The flushing of these circuits rinses the system ofendotoxins and biofilm that remain in the system after disinfect iscomplete.

Each of the remaining states are alternative pathways of the flow paththat allow certain segments to be drained. The subsequent states will beperformed for a percentage of the time or a percentage of fluiddelivered. The Dialysate Circuit Drain 7105 state flushes fluid out todrain from the dialysate circuit, while recirculating fluid in the bloodtubing set. The Fluid Prep Circuit Drain state 7106 flushes fluid out todrain from the fluid preparation circuit, while reverse recirculatingfluid in the blood tubing set. The Ultrafilter Recirculation state 7107recirculates fluid through the ultrafilter flush port, whilerecirculating fluid in the blood tubing set. The Blood Circuit Drainstate 7108 flushes fluid out through the blood circuit to drain. TheDialysate Tank Upper Level state 7109 maintains the dialysate tank at afull level. Cycling the fluid level in the tank up and down acts torinse the tank. The Dialysate Tank Lower Level state 7110 maintains thedialysate tank at a near empty level.

The Empty Tank state 7111 removes any residual dialysate from thedialysate tank by sending it to drain. The Occlusion Recovery state 7112notifies the user that an occlusion has been detected, but does not stopany flows. The Pause state 7113 will halt operation. Additionally, thepatient can choose to perform additional activities. The patient willhave the following options: Replace Components (ultrafilter orDialyzer/blood tubing set), Take Samples (RO Sample), Restart Recycling,Power Standby, and Shutdown.

(5) Treatment Preparation

The Treatment Preparation application performs a series of actions thatprepare the system to perform a dialysis session. During thisapplication, the chemical concentrates are installed, dissolved, andmixed to produce the prescribed dialysate composition. The system alsotests the integrity of the ultrafilter, the dialyzer and blood tubingset, as well as key valves, pumps, and pneumatics. Fresh dialysate isused to fully prime the system, and then flush the blood tubing set anddialyzer. Further during this application, the clearance of the dialyzerand the transmembrane pressure of the ultrafilter are tested, and theprotective systems are self-tested by simulating trigger conditionsthrough electrical offsets.

When the user requests that a dialysis session be initiated, the systemwill allow the user to collect any scheduled samples. The user is alsoprompted to install their prescribed chemical concentrate cartridge. Tomitigate possible user errors, the system prompts the user to verifythat their chemical concentrate cartridge matches their prescription.Furthermore, the system checks to ensure that the cartridge is presentand installed properly once the user indicates it to be so.

Reverse osmosis water is added to the powder chemicals and they areagitated to uniformly dissolve them. Once the powder chemicals aredissolved, they are mixed with the acid concentrate and the conductivityof the finished dialysate solution is checked against the expectedconductivity. Acceptable dialysate is routed to the dialysate tank whileunacceptable dialysate is routed to drain.

While the dialysate is being mixed, a series of integrity tests areperformed. In each case, the component under test is pressurized andthen isolated, while the pressure decay is measured over time. Ifpressure escapes too quickly, the component fails the test and should bereplaced. The dialyzer, blood tubing set, and ultrafilter are generallyreplaced by the user, while other items are generally replaced byservice personnel. The functionality of the blood line clamps isverified to ensure that the system can successfully isolate the patientfrom the machine in the event of a hazard detection. Daily integritytesting of the ultrafilter is desirable because repeated heatdisinfection and high pressure flow may damage the filter fibers. If theultrafilter fails integrity testing, endotoxins may be presentdownstream, including the dialyzer and blood tubing set. Therefore, allthree components should be replaced in this case. Next, daily integritytesting of the dialyzer and blood tubing set is desirable becauserepeated treatments and heat disinfections may damage these disposables.A broken dialyzer fiber could cause a blood leak out of the blood sideof the dialyzer and into the system and/or compromise its ability toprevent endotoxins from crossing from the dialysate side of the dialyzerand into the blood.

Key valves, pumps, pneumatics, and various replaceable cartridges aretested using pressure and vacuum tests. Either a pressure or a vacuummay be delivered to the component in test and then isolated while thepressure decay is measured over time. If pressure escapes too quickly,the component fails the test, indicating that it should be replaced.

The system is primed with the fresh dialysate. The dialyzer clearance ismeasured to determine whether its solute removal performance isacceptable. As the dialyzer is reused, the fibers can become cloggedwith blood clots and biofilm, reducing the effective surface areaavailable for solute transfer (diffusion and convection). As thishappens, the dialyzer's ability to “clear” the blood of toxins isreduced, hence the term clearance. If the clearance value has declinedmore than the allowable prescribed percentage, the operator may benotified and replacement may be performed following the completion oftreatment.

The ultrafilter transmembrane pressure (TMP) may be tested daily toensure that it does not exceed the maximum operating limit. The TMPlimit is typically a manufacturer's specification used to prevent damageto the ultrafilter fibers or housing, which could lead to an externalleak or endotoxins crossing the ultrafilter. Over time, the ultrafiltergradually becomes clogged with biofilm and other debris which causes thepressure drop across its fibers to increase. The TMP test sends themaximum system flow rate used through the ultrafilter and measures thepressure drop. If the pressure drop exceeds the maximum operating limit,the ultrafilter should be replaced following the completion oftreatment.

The reverse osmosis water in the dialyzer and blood tubing set should bereplaced with physiological fluid prior to treatment in order to preventhemolysis. Further, any residual ethylene oxide (ETO) that may bepresent in the dialyzer prior to treatment should be flushed out inorder to prevent First Use Syndrome-1 (FUS-1). Since dialysate is amicrobial growth medium, the blood tubing prime is late in theapplication process to reduce stagnant time in the set.

Protective system self tests may be performed. This is accomplished bycreating offsets in safety sensors to simulate unsafe conditions andthen confirming that each protective system reacts as intended.

FIG. 72 shows an exemplary implementation of the Treatment Preparationapplication. Referring to FIG. 72 , states of the Treatment Preparationapplication 7201 are described. The Chemical Concentration Replacementstate 7202 will perform the necessary operations to allow the user toconnect the chemical concentrates to begin the process for preparing thedialysate. This state will indicate when the machine is ready to receivethe chemical concentrates. Also during this time, the system will verifythat the chemical concentrate containers are present and connectedproperly. During the Chemical Installation state 7203, the system willprompt the user to install the chemical concentrates when it indicatesit is ready. Included in the prompt may be instructions on how toperform the installation. The system may display an instructional promptto install the chemical concentrates whether they are in a cartridge orbottle form. The operator may confirm installation by indicating theirprescription using the user interface. The Chemical Presence Test 7204detects whether the chemicals have been installed properly in thesystem. The system may verify that the chemicals have been installed byusing a presence sensor to detect whether the chemicals have beeninstalled or not. If the system indicates that the cartridges are notpresent, the system will transition to Connection Recovery 7205. Inaddition, the system monitors whether the chemical bypass door isopened, which implies that the chemical tubing is connected. Theconnections may also be verified by drawing a vacuum on the chemicalcontainer to confirm that the chemical addition ports are not open toatmosphere. Connection Recovery 7205 will handle the user interaction inthe event that the system detects that the chemical concentrates are notinstalled properly. This recovery need only be performed in the eventthat the system is unable to detect the presence of the chemicalconcentrates or the vacuum integrity test fails. When the systemindicates that the chemical concentrates are not installed properly, thesystem will instruct the user to verify that the chemicals are properlyinstalled and that all connections are securely fastened. The systemwill then wait for the user to indicate that the connections have beenchecked and allow the system to perform the Chemical Presence Test 7204again.

Upon successful completion of the Chemical Presence Test 7204, thesystem will transition to Chemical Dissolution and Integrity Tests 7206.During the Chemical Dissolution and Integrity Tests state 7206, thesystem will start the process of dissolving and combining the chemicalconcentrates to achieve the prescribed dialysate prescription. Inaddition, this state will perform routine daily integrity tests of theparticular components. The actions of Dialysate Preparation andperforming the Integrity Tests will be performed by the systemconcurrently to use time more efficiently.

The Integrity Tests state 7207 will handle the integrity testing of theUltrafilter, Blood Tubing Set and Dialyzer, and the dialysate circuit.The Ultrafilter (UFTR) Integrity Test 7208 verifies the integrity of theUltrafilter. The water in the housing is forced out, and then the air ispressurized and held against the fibers from the outside. If theallowable decay limit is exceeded, the filter should be replaced. Duringthis state, in the event that the UFTR integrity test returns anindication that the test has failed, the system will relay thisinformation to the user. The user will be instructed to Replace the UFTRvia the transition to Replace Components. Upon completion of theinstallation of the new ultrafilter, the system will re-perform theintegrity test and resume normal operation. The Blood Tubing Set(BTS)/Dialyzer Integrity Test sub-state 7209 is intended to test theintegrity of the Blood Tubing Set and Dialyzer. This is accomplished bygenerating a pressure, and then measuring the decay. If thedialyzer/blood tubing set fails the integrity test, the user is notifiedto replace the dialyzer and blood tubing set. During this state, if thesystem returns a Failed status for the BTS and/or Dialyzer Integrity,the system will notify the operator that the BTS and/or DialyzerIntegrity test failed. The user will be provided with information andthe ability to replace these components through the Replace Componentsoption. Once the component(s) have been replaced, the system willre-perform the integrity test. If desired, a general system integritytest may be performed during a Valves/Pumps/Pneumatics Integrity state7210.

The Integrity Test Failure Recovery state 7211 provides instructions tohandle any integrity test failures identified during the integritytests. If the system indicates that there was an integrity test failure,the user will be notified by the system of the failure, as well whichcomponent failed. The user may then perform the necessary actions toperform the replacement. Upon the user's indication that the newcomponent has been installed, the system will resume normal operation.

The System Prime with Dialysate state 7212 will perform the necessaryactions to prime the system with dialysate. This state includes a Primewith Dialysate state 7213, a Dialyzer Clearance state 7214, anUltrafilter Transmembrane Pressure (UFTR TMP) state 7215, and a FlushETO Prime state 7216. The Prime with Dialysate state 7213 beginschemical production and primes the system with dialysate. The DialyzerClearance state 7214 quantifies the amount of sodium clearance, used asa surrogate for urea clearance, that can pass across the dialyzermembrane under given flow rate and temperature conditions. The UFTR TMPstate 7215 measures the transmembrane pressure (TMP) across theultrafilter at the maximum system flow rate, to ensure that is does notexceed the specified maximum ultrafilter TMP. In the event that the UFTRTMP exceeds the acceptable limit, the system may continue with itsnormal operation. The user will be notified that the ultrafilter (UFTR)requires replacement due to a failed TMP test and that the replacementwill be performed during Recycle Preparation. The Flush ETO Prime state7216 flushes the dialyzer of ethylene oxide (ETO) that may have leachedout.

During the Sample Notification state 7217, the system will identify ifany samples have been previously scheduled by the patient or clinicalrepresentative. This state also notifies the operator of the samplesscheduled. The following are samples that the operator may be notifiedto collect: Blood Samples, Chlorine Sample/Test, ChloraminesSample/Test, and RO Water Sample. During the Perform Sample state 7218,the system will notify the user that there are samples scheduled to betaken. During this state, the user will have the opportunity to acceptor decline taking these samples. The system will evaluate whether thereare samples scheduled or not. If the system indicates that there aresample(s) scheduled and the user elects to perform the sample, thesystem will transfer responsibility to Pause 7219, where each of thesamples will be handled.

The system will create conditions that allow self-testing of theprotective systems before a patient is connected to the machine. Uponthe detection of a protective systems test failure, the ProtectiveSystems Tests state 7220 will initiate corrective action if applicable.The following protective systems may be tested prior to patientconnection: Air Detection (Venous and Arterial), Dialysate Conductivity,Dialysate Temperature, Blood Leak Test, Fluid Leak Test, and Doors Open.This may be accomplished by offsetting each of the sensors to simulate acondition where the protective system will trigger. The system willconfirm that the proper protective system was initiated.

The Protective Systems Test Failure Recovery 7221 is triggered in theevent that one of self tests returns a failed status. This state isentered upon the completion of all of the Protective System Tests 7222.In the event that any of the Dialysate Conductivity Protective SystemTest, Dialysate Temperature Protective System Test, Blood LeakProtective System Test, and Fluid Leak Protective System Test return thefailed status, the operator may be instructed that operation cannotcontinue. In the event that either of the Air Detection ProtectiveSystem Test or the Door Protective System Test return the failed status,the operator may be instructed to perform the corrective actions relatedto the failure.

(6) Patient Connect

Following the treatment preparation, the patient connection to thesystem is made and the extracorporeal blood tubing circuit is primedwith blood. There are at least two priming prescription options: thefirst method is “Prime Discarded” (or Prime Not Returned) where thedialysate priming solution is drawn into the machine as blood isintroduced into the extracorporeal circuit. The second method is “PrimeReturned” where the dialysate priming solution is given to the patientas blood is introduced into the extracorporeal circuit. Choice of thesetwo methods depends on how much volume the patient wants to removeduring the priming process and whether their venous access can toleratefluid being drawn from it.

For Prime Discarded, blood is drawn from the patient's arterial andvenous access sites simultaneously into the machine as the primingsolution is discarded to drain. This priming method is often preferred,because patients typically begin dialysis treatment volume overloadedand therefore wish to accomplish priming without taking on additionalfluid. The user may chose to switch priming methods to Prime Returned iftheir access cannot tolerate the reverse flow up the venous line. Thearterial and venous flow rates may be matched as closely as possiblesuch that the blood fronts just meet inside the dialyzer fibers. Theextracorporeal circuit may be purposefully slightly “underprimed” inorder to avoid localized hemoconcentration that could occur if the bloodis ultrafiltrated during the priming process.

For Prime Returned, blood is drawn up the arterial line and the primingsolution is displaced down the venous line to the patient. This primingmethod may be prescribed for those patients whose accesses cannottolerate the reverse flow up the venous line used during PrimeDiscarded, or who are sensitive to hypovolemia. If the patient cannottolerate losing volume quickly, this method allows them to keep theirvolume during prime.

Additionally, if the patient still needs extra volume, they can initiatea solution infusion any time they are connected. Especially for patientswho are sensitive to hypovolemia, they may choose to start treatmentwith a slight excess of fluid.

For either priming method, the operator may choose to change the primingblood flow rate at any time. However, any changes do not affect theprescribed setting for the subsequent treatment. Access site compromiseand pressure/flow problems are common at the initiation of treatment,and therefore the operator may wish to slow down the blood flow rateduring priming.

While the dialyzer and blood tubing set have already been flushed tomatch the dialyzer manufacturer's instructions sheet, there is anindustry concern about further leaching of sterilant out of dialyzerswhen they sit with fluid stagnate in them. Therefore, if the dialyzersits stagnant for too long, it may be re-flushed.

FIGS. 73 a-d show an exemplary implementation of the Patient Connectapplication. With reference to FIG. 73 a , the Connection and Primingstate 7302 of the Patient Connection application 7301 allows the patientto take a priming sample if scheduled, connect to the machine, and primethe blood tubing set with blood. Within the Connection and Priming state7302, the Connection state 7303 encompasses taking a priming sample andconnecting to the machine. During this state, the system may determinewhether the priming solution has expired. For brand new dialyzer,priming solution expires approximately 15 minutes after the last flushof dialyzer and blood tubing set. For a dialyzer that has at least oneheat disinfect, priming solution may expire approximately 30 minutesafter the last flush of dialyzer and blood tubing set.

There is an industry concern about leaching of sterilant out ofdialyzers when they sit with fluid stagnant in them. Therefore, if theprevious flush of the dialyzer occurred 15 minutes ago for a newdialyzer, or 30 minutes ago for a dialyzer that has one or moredisinfects, the dialyzer may be re-flushed. This flush will remove anyresidual ethylene oxide (ETO) that may be present in the BTS in order toprevent First Use Syndrome-1 (FUS-1). The rationale for differing timesbetween a brand new dialyzer and a dialyzer with one or more heatdisinfects is that a brand new dialyzer will likely have more ETO thatcan leach out. A used dialyzer will have little or no residual ETO.

The Collection Decision state 7304 determines whether a priming sampleis scheduled or not, based on certain database items. The Connect toMachine state 7305 prompts the patient to enter their weight and connectto the machine. It waits until they indicate they are connected. Thestate will post a message indicating the connection procedure and themeans for entering patient weight. If heparin is prescribed, it willalso prompt the patient to load a heparin vial into the pump.

The Priming Sample Collection state 7306 allows the patient to collect apriming sample. The priming solution sample is used to perform amicrobiological evaluation of the dialysate fluid used to prime thedialyzer and blood tubing set. Within the Priming Sample Collectionstate 7306, the Prompt for Sample state 7307 prompts the patient tocollect a priming sample. The Deliver Sample state 7308 pushes fluidacross the dialyzer and out the venous line, providing the patient witha sample of the priming solution. A notice may be provided to thepatient allowing them to terminate sample collection at any time.

The allowable volume for a priming solution sample may be 500 ml, forexample. Typically, a sample of 150 ml is needed for microbiologicalevaluation. Sterile sample collection generally requires that some fluidflow into a waste container prior to taking the sample. A maximum volumeof 500 ml also allows the user to take an additional sample if the firstsample gets contaminated. The request for sample collection duration maybe approximately 30 seconds or less. To obtain a 150-ml sample, thedesired flow rate from the venous line may be 300 ml/min. The dialysatemay be heated to the prescribed temperature in preparation for primingwith blood. Should the patient elect to receive the dialysate prime inthe blood tubing set, it will be a comfortable temperature.

The Stop Collection state 7309 stops fluid flow and waits for themachine stop to be completed. This state is entered either due to asample volume limit being reached, or due to patient request. When themachine has stopped, a Collection Stopped event 7310 is triggered,causing a transition to the Collection Stopped state 7311. TheCollection Stopped state 7311 waits for the patient to indicate they areready to move on to connection. Alternatively, the patient may requestadditional sample collection.

The Reprime state 7312 ensures the patient reconnects the blood tubingset and closes the doors. The dialysate and blood tubing set are thenre-flushed. The Close Doors state 7313 prompts the user to close thedoors. Referring to FIG. 73 b , The Doors Wait For Stop state 7315issues a stop command and waits for the machine to stop. The Doors WaitFor User state 7316 waits for the common monitoring application toindicate that the doors are closed, either because the user or adetector indicated that the doors are closed. The Repriming blood tubingset state 7314 re-flushes any residual ETO that may have leached outduring a period of inactivity.

Referring again to FIG. 73 a , the Dialysate Production Recovery state7317 allows the machine to recover from a scenario where the dialysatetemperature is out of specification. Once the temperature of thedialysate is within 1° C. of the prescription temperature, for example,the process may transition to the Reprime state 7312.

The Prime With Blood state 7318 primes the blood tubing set and dialyzerusing either the Prime Returned 7319 or Prime Not Returned 7320 method.If a blood leak is detected, an alarm event is generated. The Prime NotReturned state 7319 primes the blood tubing set by pulling blood up boththe arterial and venous lines, and displacing the dialysate through thedialyzer and down to drain. The system may notify the patient that atany time during the state they can select Prime Returned 7320 or modifythe priming blood flow rate. The arterial priming rate is a prescriptionitem and may be modified by the patient. The blood tubing set anddialyzer volume may be slightly less than nominal in order to reflectdialyzer bundle volume decreases over time and also to avoidhemoconcentration. The Monitor Prime Not Returned state 7321 monitorspriming of the blood tubing set by checking the status of the primingprocess.

The Stop Discard Prime 7322 state stops fluid and waits for the machinestop to be completed. When the machine has stopped, the Discard Stoppedevent 7323 is triggered, causing a transition to Prime Returned 7320.The Prime Returned state 7320 primes the blood tubing set by pullingblood up the arterial line and displacing dialysate down the venous lineto the patient. Arterial air may be monitored. The patient may benotified of the ability to modify the priming blood flow rate at anytime during the state. The Start Prime Returned state 7324 startspriming the blood tubing. While blood is being drawn up the arterialline, the priming solution will be given to the patient through thevenous line. Rate is a prescription item and may be modified by thepatient. The Monitor Prime Returned state 7325 monitors priming of theblood tubing set by accumulating the total volume pumped and comparingit to the total volume in the dialyzer and blood tubing set. When thevolume pumped is greater than total dialyzer and blood circuit volume,priming is complete. If the patient started Prime Not Returned 7319, theamount primed during that state will be carried forward to this state.The patient is notified when they can begin treatment. If the patientindicates they are ready to begin treatment, the Patient Connectionapplication is stopped and the Dialyze Application will be started.

The Air Recovery state 7326, shown in FIG. 73 c , allows the user torecover from air intrusion into the blood tubing set. The Air Wait forStop state 7327 waits for the flow to stop. The Air Wait For User state7328 waits for the common monitoring application to indicate that thealarm is cleared.

The Occlusion Recovery state 7329 notifies the user that an occlusionhas been detected, but does not stop any flows. Within the OcclusionRecovery state 7329, an Occlusion Wait For Stop state issues a stopcommand and waits for the machine to stop. An Occlusion Wait For Userstate waits for the common monitoring application to indicate that theocclusion is cleared.

Referring to FIG. 73 d , the Pause state 7330 is shown in detail. ThePause state 7330 will halt operation. Additionally, the patient canchoose to perform additional activities. In particular, the patient mayhave the following options: Take RO Sample, Resume Active, Rinseback,Disconnect, Power Standby, and Shutdown. Since the Pause state 7330,does not have history, the state machine transitions to Pause Wait ForStop 7331, which issues the stop functions. Again, if the patientselects to resume operation, the process returns to the Connection AndPriming state 7302, which dispatches to the prior sub-state(s) via ahistory mechanism. When the user selects a Pause button, the UserRequests Pause event 7332 may be sent, causing the Patient Connect statemachine to transition into Pause and then into the initial state PauseWait For Stop. The entry action on Pause Wait For Stop calls the machinestop functions. Once the machine has stopped, the state machinetransitions to Pause Wait For User Choice 7334. If the user selectsResume, the event User Requests Resume 7333 is accepted.

If the patient chooses to run another application, such as the ReplaceComponents Application 7335, the Master Control triggers the PatientConnect Stop event 7336, causing the Patient Connect state machine totransition to the Idle state 7337. Once the machine has stopped, thestate machine transitions to Pause Wait For User Choice 7334. When theUser Requests Resume event 7333 is triggered, e.g., by the user pressingthe resume button, the state machine transitions back to Connection AndPriming 7302, and will resume according to the history within that stateand its sub-states.

Referring again to FIG. 73 a , the Nonrecoverable Alarm 7340 statenotifies the patient that there is an unrecoverable alarm. The currentapplication stops, and the patient may be instructed to disconnect fromthe system after acknowledging the alarm.

(7) Dialyze

Following connection to the dialysis unit, dialysis therapy may bedelivered to a patient. Dialysis therapy removes toxins and excess fluidfrom a patient's blood, using diffusion, forward ultrafiltration andbackward filtration (convection). In addition, heparin may beadministered to the blood to prevent coagulation during treatment.

Diffusion is accomplished by exposing the patient's blood to a dialysatesolution through a semi-permeable membrane. Blood may be drawn from thepatient's arterial access and returned to their venous access.Simultaneously, fresh dialysate may be produced from reverse osmosiswater and chemical concentrates, heated to the prescribed temperature,and delivered to the dialysate side of the dialyzer while spentdialysate is routed to drain. The concentration gradient at the dialyzermembrane causes toxins of various molecular sizes to equilibrate, bymoving from the blood into the dialysate. The prescribed blood anddialysate flow rate settings and their accuracy is important inachieving the desired amount and rate of toxin removal. The flow of theblood and dialysate is countercurrent in order to maximize theconcentration gradient at all points, increasing the amount of diffusionthat will occur. Diffusion is also enhanced by the fact that dialysatedelivered to the dialyzer is fresh rather than recirculated. Furtherfactors that may affect dialysis therapy dose delivered include patientsize, prescribed treatment duration, dialyzer effective surface area anddialyzer clearance.

Forward ultrafiltration removes excess fluid from the patient's blood.The prescribed fluid volume is removed by generating a lower pressure onthe dialysate side of the dialyzer, thereby pulling fluid from theblood. The ultrafiltration rate is calculated using the prescribed fluidvolume to be removed and also takes into account any dialysate volumesdelivered to the patient during the priming, backflushing, and rinsebackprocesses.

Backward filtration, or backflushing, is the inverse of forwardultrafiltration. Instead of pulling fluid from the blood side of thedialyzer to the dialysate side, fluid is pushed from the dialysate sideto the blood side. This process helps to prevent clot formation withinthe blood tubing and dialyzer, which in turn may allow for a smallerheparin dosage, prolong the useful life of the dialyzer, and facilitatedialyzer cleaning and re-use. Backflushing has the additional benefit ofpromoting better solute removal through convection. Like diffusion,convection removes toxins from the blood. But unlike diffusion, whichrelies on a concentration gradient, convection relies on the activemovement of fluid across the dialyzer to carry solutes. Backflushing iscontrolled by the synchronization of the blood and dialysate portions ofthe flow path. By changing the phase between blood and dialysate sides,there is constant and repeated shifting of fluid across the dialyzer insmall increments. This shifting of fluid pushes dialysate into the bloodcircuit and then pulls it back, but results in no net ultrafiltration.

While dialysis is occurring, heparin may be administered. Thisadministration can be handled either as a series of one or more bolusesof fluid, or on a continuous basis. The patient may also choose toreceive an additional bolus or boluses of heparin in the event thatunexpected coagulation occurs.

FIGS. 74 a and 74 b show an exemplary implementation of the Dialyzeapplication. Referring to FIG. 74 a , the Dialyze state 7401 is the toplevel state that coordinates the actions that lead to the overalldialysis therapy. This state runs concurrently with the data handlingelements of the state machine. During this state, dialysate will beproduced and an adequate buffer will be maintained in the dialysatetank. Updates to data of interest to the dialyze application will beprocessed by the data handling elements of the state machine.

The Active state 7402 of the dialyze application is where all dialysisrelated processing occurs. Dialysis is complete when the dialysis timeremaining expires. The Monitor state 7403 is responsible for initiatingthe blood and dialysate flow rates so that treatment can be performed.Blood leak monitoring and air monitoring may be requested, andultrafiltration monitoring may be enabled. The Initial Blood Flow state7404 starts the blood pump at a low rate in order for the patient tocheck their access before starting treatment. The Start Blood andDialysate Flow state 7405 increases the blood flow rate to theprescribed flow rate. It also starts dialysate flow by heating the fluidfrom the dialysate tank and diverting it around the dialyzer.

The Dialysis and UF Control state 7406 is responsible performinghemodialysis. Dialysis will occur with ultrafiltration and heparinadministration. A dialysate temperature alarm may be generated if thetemperature is not within acceptable limits. Complete blood sideocclusion monitoring may be is requested, and partial blood sideocclusion monitoring may be requested to stop. The Steady State Dialysisstate 7407 performs dialysis by circulating blood and dialysate throughthe dialyzer. It also collects certain treatment related information.The Partial Occlusion state 7408 notifies the user that an occlusion hasbeen detected, but does not stop any flows. The Administer Heparin state7409 will administer heparin at a prescribed rate. Heparin will bestopped if the amount of heparin delivered is equal to the prescribedamount or the patient requests that heparin delivery be stopped. TheHeparin Bolus state 7410 will deliver a bolus of heparin.

The Ultrafiltration state 7411 performs ultrafiltration. Theultrafiltration rate is determined by taking the amount of fluid neededto be removed divided by the time remaining in the treatment. If thetarget ultrafiltration volume differs by more than 500 ml from thecurrent ultrafiltration volume, an ultrafiltration alarm may result. Ifeither of the following is true, ultrafiltration may be stopped: (1) theamount of ultrafiltration is greater then or equal to Prescribed volumeneeded to be removed+Rinseback Volume+Priming Volume, or (2) the patientrequests ultrafiltration to stop and the amount of ultrafiltration isgreater then or equal to the Rinseback Volume+Priming Volume. A countingalgorithm may be used to compare the actual strokes of theultrafiltration (“UF”) pump with the predicted number of strokes toachieve the target volume of ultrafiltrate. The expected number ofstrokes can be synthesized based on the requested volume and rate ofultrafiltration. The actual strokes of the pump can be counted by havingthe controller monitor the valve states of the ultrafiltration pump. Inone implementation, if the actual strokes exceed the expected strokes bygreater than a safety threshold, the machine can be placed in a safestate. If the actual strokes fall behind the expected strokes by athreshold amount, the pumping rate or duration can be extended to avoidhaving the treatment session undershoot the desired ultrafiltrationamount.

The Recirculate Blood and Dialysate state 7412 recirculates blood anddialysate, with dialysate bypassing the dialyzer, in order to bring thetemperature of the dialysate into treatment limits.

The Occlusion Stopping state 7413 stops blood flow if the blood flowrate drops too far notifies the user that a problem exists. When noocclusion is detected in the Occlusion state 7414, the machine willcontinue to the Initial Blood Flow state 7404.

The Air Recovery Stopping state 7415 notifies the user that airintrusion into the blood tubing set has occurred and waits for thefunction to stop. The Air Recovery state 7416 allows the user to recoverfrom air intrusion into the blood tubing set.

The Pause Monitor state 7417 is responsible for pausing the device anddisplaying pause menu options. Referring to FIG. 74 b , the MonitorStopping state 7418 will stop the device and give visual feedback to theuser that the pause button was processed. The Pause Monitor Optionsstate 7419 will display all the Pause menu options. The MonitorDisconnect application 7420 will wait in the state to be stopped bymaster control. The Monitor Solution Infusion application 7421 will waitin the state to be stopped by master control. The Monitor Take Samplesapplication 7422 will wait in the state to be stopped by master control.The Monitor Power Standby application 7423 will wait in the state to bestopped by master control. The Monitor Shutdown application 7424 willwait in the state to be stopped my master control.

Referring again to FIG. 74 a , the Data Handler Init state 7425 isresponsible for initializing all the data of interest for the Dialyzeapplication. Upon completion of this initialization it will generate aDialyze Launch Ok event 7426 to indicate to Master Control theapplication is ready to be started. The Update Data state 7427 isresponsible for maintaining up to date values or all the data ofinterest for the Dialyze application.

(8) Solution Infusion

To counteract a hypotensive event, the system may deliver a bolus offluid volume to a patient. As the system removes fluid volume from thepatient during treatment, it is possible that an unexpected drop inpatient systemic blood pressure may occur. This hypotensive event canlead to patient lightheadedness, fainting, or even more seriouscomplications. To prevent these outcomes, the user need only request asolution infusion. The system may then deliver a prescribed bolus ofultrapure dialysate.

Once the user has requested a solution infusion, the blood pump may beleft running to prevent clotting. The Solution Infusion application willassess whether there is enough dialysate volume available to deliver theinfusion and still have enough reserve volume to rinse back thepatient's blood. If not, the user may be notified that infusion is notpossible, and may be instructed to either select rinseback or resumetreatment. If there is enough dialysate, a short countdown be displayedto the user prior to starting the infusion. Since solution infusion isavailable via a single button press, it is possible that the user mayhave pressed the button in error. This delay gives them the opportunityto cancel the infusion before it begins.

Following the delay, fresh, heated dialysate fluid is sent across thedialyzer and down the venous line to the patient. At the same time, theblood pump is slowly run forward to continue circulating blood andprevent clotting. In order to deliver relief as quickly as possible, theflow rate used for the infusion is as fast as reasonably tolerable bymost patients' accesses and vasculature. A flow rate that is too highmay create high pressures in the blood tubing set and lead to nuisanceinterruptions of the infusion delivery. Further, the infusion flow rateapproximates the flow from a saline bag that a nurse might hang tocounteract a hypotensive episode on other devices.

After the prescribed solution infusion volume has been delivered, if thepatient continues to experience hypotensiveness, they may choose toinfuse smaller additional boluses as long as enough dialysate volume isavailable. Once the patient leaves this application and returns back tothe previous activity (e.g., Patient Connect or Dialyze), subsequentrequests for a solution infusion may be for the full prescribed solutioninfusion volumes.

FIGS. 75 a-e show an exemplary implementation of the Solution Infusionapplication. With reference to FIG. 75 a , Solution Infusion 7501 is thetop level state which coordinates the actions that lead to the deliveryof a solution infusion. This state runs concurrently with the datahandling elements of the state machine. Updates to data of interest tothe Solution Infusion application will be processed by the data handlingelements of the state machine. The Idle state 7502 is the state of theSolution Infusion application during all other system processing. Uponreceiving a Solution Infusion Start event 7503 the Solution Infusionapplication will transition to the Active state 7504. The SolutionInfusion application will indicate it has started when transitioning tothe Active state. Upon receiving a Solution Infusion Clear History event7505, the Solution Infusion application will clear the history andremain in the Idle State 7502. During the Active state 7504 of theSolution Infusion application, the solution infusion volume to bedelivered is set.

The Monitor state 7506 watches for common hazards, such as Blood Leak7507, Arterial and Venous Air 7508, and Occlusion 7509. The Monitorstate 7506 starts the monitors by sending events to the monitoringprocess, and Starts dialysate production in case it has been stopped bya Pause or other interruption.

The Delay for Possible Cancellation state 7510 allows the patient tocancel the Solution Infusion if they choose. During the delay (e.g., 3seconds), the user interface may give the user an updating visualindication of the time until the infusion will start and the ability tocancel the infusion. If the delay elapses without cancellation, theDelay Done 7511 event will occur.

The Fluid Delivery Evaluation state 7512 evaluates whether there issufficient dialysate available to deliver the requested infusion. Italso calculates the solution infusion volume to be given in the InfusingFluid state. The Fluid Unavailable state 7513 will notify the patientthat there is not enough fluid to perform the requested infusion. Theblood pump will continue to circulate while the patient responds. Ifthere is sufficient fluid, the Stop Circulation state 7514 will stop thecirculation of blood so that the solution infusion may begin.

The Infusing Fluid super-state 7515 encapsulates the behavior of theapplication while the solution infusion machine layer command isrunning. The solution infusion operation pushes ultrapure dialysateacross the dialyzer and down the venous line to the patient. Dialysateis heated before it is pushed across the dialyzer. At the same time, theblood pump is slowly run forward to minimize blood clotting. The volumeof fluid left to be infused may be updated during this state. A staticvariable representing this volume may be initially set in the FluidDelivery Evaluation state 7512 and then updated in this state as volumeis accumulated in the machine layer status variable, Dialysate CircuitVolume. The volume to be infused should be decremented by the deliveredvolume. If the Dialysate Temperature Out of Spec 7516 event occurs, thetransition will be to the Dialysate Temperature Recovery state 7517. Ifthe volume to be infused is less than 25 ml due to interruption andre-entrance, the Pump Stopped event 7518 may be immediately issued andno infusion should be given.

In the Start Infusing state 7519, the solution infusion machine layercommand is started. The volume to be infused is being continuallyupdated as volume is delivered so that the correct volume is enteredwhenever the infusion is started or restarted. When the machine layerstatus indicates that the command has been started, the SI Started event7520 is issued to cause the transition to the next state.

The Dialysate Temperature Recovery state 7517 allows the machine torecover from a situation in which the dialysate temperature is out ofspecification. Dialysate is routed directly to the drain, while thetemperature is monitored for a return to its acceptable range. If thetemperature of the dialysate is within the target range for fiveconsecutive readings, for example, the recovery is complete and theDialysate Temperature Recovered event 7521 is issued.

The Completion super-state 7522 starts blood circulation to preventclotting, and waits for the patient to either indicate they would likean additional infusion, or that they are done with infusions. If a Pauseoccurs during any state within this super-state, the Pause state 7523will stop the circulation. Upon returning from Pause, circulation willbe restarted and the user will again be asked whether an additionalbolus is required. The Wait for Response state 7524 waits for thepatient to either indicate they would like an additional infusion, orthat they are done with infusions. If no further infusions are desired,this application is ended. The patient will be notified by the userinterface that Solution Infusion is complete and they have the option ofperforming additional bolus infusions. If the user indicates that anadditional infusion is needed, the local variable solution infusionvolume may be set to deliver equal to 100 ml and transition to the FluidDelivery Evaluation state 7512.

Referring to FIG. 75 b , the Air Recovery state 7525 allows the user torecover from air intrusion into the blood tubing set. The machine layerfluid delivery function will be stopped, the user will be notified thatair is present, and the application will remain in this state until theuser indicates that the air has been cleared and the sensors do notdetect air. The state machine history will return the application to thestate that was interrupted. Following the Air Wait for Stop state 7526,the Air Wait for User state 7527 notifies the user that air is presentin the blood tubing and provides instruction for removing the air, thenwaits for the user to indicate that the air is no longer present. Whenthe user indicates that the air has been removed, the application willtransition to the Recheck Air state 7528.

Referring to FIG. 75 c , The Occlusion Recovery state 7529 notifies theuser that an occlusion has been detected and waits for the user torespond. Following the Occlusion Wait for Stop 7530, the Occlusion Waitfor User state 7531 notifies the user that an occlusion is present inthe blood tubing and provides instruction for removing the occlusion,then waits for the user to indicate that the occlusion is no longerpresent.

Referring to FIG. 75 d , the Pause state 7523 will halt operation.Additionally, the patient can choose to perform additional activities.When the Pause operation has finished and the user chooses to resumethis application, the history mechanism will return this application tothe interrupted state. Following the Pause Wait for Stop state 7532, thePause Wait for User Choice state 7533 presents options for the user andwaits for the user to choose an option. In particular, the followingoptions may be presented: Rinseback 7534, Patient Disconnect 7535,Resume Treatment 7536, Interrupt Treatment 7537, Power Standby 7538, andResume Solution Infusion 7539.

Referring to FIG. 75 e , the Blood Leak state 7540 stops the currentoperation in state 7541 and notifies the patient that there is anonrecoverable alarm in state 7542.

(9) Rinseback

The Rinseback application implements the process of returning thepatient's blood and guiding the patient through disconnection from theextracorporeal circuit. This process occurs at the end of treatment.Treatment may end once the prescribed dialysis duration has elapsed, atany time as requested by the user, or due to a hazard detection by thesystem.

When the patient has requested that their blood be rinsed back, thesystem begins sending fresh, heated, ultrapure dialysate across thedialyzer to send the blood back to the patient. At the same time, theblood pump is run slowly in reverse such that both the arterial andvenous lines clear simultaneously. The prescribed rinseback volumeincludes the total volume of the blood tubing set and dialyzer plusadditional dialysate volume to flush the patient access and rinse thetubing lines clear of nearly all blood traces.

After this volume has been delivered, the user may choose to infuse anadditional smaller rinseback bolus. This may be done to counteractpatient hypotensive sensations and/or return visible blood tracesremaining in the tubing. The user can request additional rinsebackboluses in 50 mL increments until, for example, the total additionalbolus volume delivered reaches 500 mL. The limit may be selected toprevent operator misuse, leading to fluid overload. Furthermore,rinseback fluid delivery may be limited by fresh dialysate availability.

In order to complete rinseback as quickly as possible, the flow rateused may be as fast as reasonably tolerable by most patients' accessesand vasculature. A flow rate that is too high may create high pressuresin the blood tubing set and lead to nuisance interruptions of therinseback process. Further, the flow rate may approximate the flow froma saline bag that a nurse might hang to rinseback blood on otherdevices.

Throughout rinseback, potential air embolism hazards exist, since bloodis flowing down the arterial and venous lines towards the patient. Ifair is detected in the arterial line, the operator will be notified, andrinseback will continue down the venous line only.

FIGS. 76 a and 76 b show an exemplary implementation of the Rinsebackapplication. With reference to FIG. 76 a , the Active state 7602 of theRinseback application 7601 is the state in which Rinseback processingoccurs. The state 7602 generates the event Rinseback Stopped 7603 ontransitioning to Idle 7604.

With reference to FIG. 76 b , the Monitor state 7605 monitors for Pauserequests 7606, venous air in the blood tubing set 7607, dialysate leaks7608, and dialysate production problems 7609.

The Administer Fluid state 7610 administers the infusion and monitorsfor occlusions, dialysate temperature out of limits, conditions ofunavailable fluid and inlet water out of limits. The Arterial and VenousInfusion state 7611 pushes ultrapure dialysate across the dialyzer.Dialysate may be heated as it is pushed across the dialyzer. Arterialair and venous air may be monitored. The Arterial Air Recovery state7612 handles a recovery from an arterial air alarm. The Stop A&VInfusion state 7613 stops the infusion and posts an alarm to the GUI.The Arterial Air Resolution state 7614 waits for the user to indicatethey are ready to continue with Venous-only Rinseback. The VenousInfusion state 7615 pushes ultrapure dialysate across the dialyzer.Again, dialysate may be heated as it is pushed across the dialyzer.

The Dialysate Tank Empty Alarm state 7616 will stop Rinseback and notifythe patient there is not enough dialysate to continue with Rinseback. Adialysate tank low alarm may be posted to the GUI. Fluid production maybe restarted, if stopped. The Wait for Fluid state 7617 waits for fluidto become available. Once the dialysate tank volume reaches a certainlevel, e.g., 300 ml, a Dialysate Tank Filled event 7618 may begenerated. If the tank has not reached the given level in a selectedperiod of time, e.g., 2 minutes, an error event may be generated.

It may be possible to improve the accuracy of liquid volumedeterminations in the dialysate tank by using at least two independentmethods of measurement. One method, for example, counts the number ofpump chamber strokes that deliver liquid to the tank, and subtracts thenumber of pump chamber strokes that withdraw fluid from the tank.Assuming that each pump stroke moves a fixed quantity of liquid, acumulative net liquid volume in the tank can be tracked. A secondexemplary method involves taking an FMS measurement by charging areference chamber to a predetermined pressure, and then venting thereference chamber to the tank. The volume of air in the tank can then becalculated from the equalized pressure between the tank and thereference chamber. Although an FMS-based method may yield more accurateresults, it may also be more time-consuming. Thus it may be desirable tohave the computer keep track of the tank volume continuously by pumpstroke accounting, and have it perform an FMS measurement periodicallyto verify the ongoing accuracy of the pump stroke accounting. Acontroller applying one or both of these methods can use this data todetermine whether fluid should be added to or removed from the tank, andwhether the fluid level is below the minimum deemed necessary to safelycontinue therapy.

Pump stroke accounting operates by polling the pumps that can deliverfluid into and out of the tank, continuously accounting for completedstrokes and discounting incomplete strokes due to occlusions. New fluidcan be supplied to the dialysate tank by the mixing pump and thebicarbonate and acid pumps, and pump strokes can be tallied only whenthe outflow valve to the tank is registered as being open and the drainvalve is registered as being closed. The state of the valves can bemonitored by reading the valve state via the I/O subsystem; or in asimpler arrangement, the valve state can be assumed according to theparticular operation being performed at the machine level. Fluid can beremoved from the dialysate tank by the outer dialysate pump when thetank drain valve is open and the tank recirculation valves are closed.The outer pump can be polled for completed strokes, and strokes can bediscounted if a chamber fill occlusion is detected. Should an occlusionbe detected with any of the pumps, the pump stroke accounting value canbe flagged as suspect or invalid, and a tank volume measurement can betaken using an independent method, for example the FMS method.

The FMS method of measuring the air (and therefore the liquid) volume inthe dialysate tank is based on Boyle's law. A reference volume ispressurized and then vented into the closed dialysate tank, the volumethen being calculated from the final pressure reached by the combinedreference and tank air volumes. This method may be prone to some errorbecause of delays in or incomplete closures of the valves thatcommunicate with the tank, or because of physical distortion of the tankunder pressure. The measurement may also take a substantial amount oftime, which could reduce the efficiency of dialysate delivery fordialysis. Thus some of the physical characteristics of the dialysatetank and valves may introduce measurement error if the classical FMSequation P1V1=P2V2 is used.

The FMS measurement method may be improved by using a third orderequation, which may increase the accuracy of the volume determination atthe target tank fluid level of 50-75%. Such an equation can take severalforms, and is based on fitting experimentally derived pressure-volumedata to a curve defined by the third-order equation. The measurement ofthe volume in the dialysate tank can be calibrated, for example, byincrementally filling the tank and performing FMS measurements on thetank at each increment. Data points are collected and a mathematicalmodel correlating the FMS data to the actual fluid volume within thetank can then be generated. For example, the controller can perform an“AutoCal” function that empties the tank, and then fills itincrementally with seven 300 ml volumes of liquid, making an FMS volumemeasurement with each incremental fill. These measurements can then beinputted in the form of a vector into a function that calculates thecoefficients for the third order equation using a least squaresalgorithm, for example, to minimize the error between the observed andpredicted volumes. The function may then update the coefficients used inthe third order FMS equation that are stored in a calibration data fileon a hard drive or in the system memory.

The Occlusion Alarm state 7619 will stop Rinseback and notify thepatient there is an occlusion, e.g., by posting an occlusion alarm tothe GUI. The Occlusion Resolution state 7620 waits for the patient toclear the occlusion.

The Dialysate Temperature Alarm state 7621 will stop Rinseback andnotify the patient the dialysate temperature is out of range, e.g., byposting a temperature alarm to the GUI. The Recirculate Dialysate state7622 allows the machine to recover from a scenario where the dialysatetemperature is out of specification. At the same time, blood maycontinue to circulate to prevent clotting. In this state, dialysate maybe routed directly to drain as the machine attempts to bring the limitswithin range.

The High Inlet Water Temp Alarm state 7623 will stop Rinseback andnotify the patient the water entering the machine is too hot, e.g., byposting an inlet water temperature high alarm to the GUI. This statediverts hot water to drain and waits for the water to reach nominaltemperature.

The Wait state 7624 is intended to handle the transitions betweenRinseback and Disconnection. This state will essentially put the systeminto an idle state. Besides handling the transitions between Rinsebackand Disconnection, this state will also control the ability to performadditional bolus infusions. The Wait for User state 7625 waits for theuser to either request an additional Rinseback or to indicate they aredone with this process. If the patient indicates they are done withRinseback, an event may be generated to terminate Rinseback.

The Venous Air Alarm state 7626 will stop Rinseback and notify thepatient venous air has been detected. The Venous Air Resolution state7627 waits for the patient to clear the air bubble and for an indicationof the same from the patient.

The Dialysate Leak Alarm state 7628 will stop operation and notify thepatient a dialysate leak has been detected. A dialysate leak alarm maybe posted to the GUI. The Leak Resolution state 7629 waits for thepatient to clear the leak and for an indication of the same from thepatient.

The Dialysate Production Alarm state 7630 will stop operation and notifythe patient a dialysate leak has been detected. A dialysate productionalarm may be posted to the GUI. The End Rinseback state 7631 waits forthe patient to acknowledge the alarm. Upon acknowledgement of the alarm,an event may be generated to end Rinseback.

The Pause Menu state 7632 allows the patient to choose to performadditional activities. The following options may be displayed andselected by a user: Patient Disconnect, Power Standby, and Shutdown.

(10) Take Samples

The Take Samples application gives the operator the ability to takecertain fluid samples. In order to safely and effectively administerdialysis treatment, it may be necessary to periodically collect samplesof dialysate and reverse osmosis water for laboratory analysis. Thisapplication allows the user to more easily collect these samples bypresenting the fluid for sampling at a convenient location forcollection.

For dialysate sample collection, dialysate is circulated through thedialyzer. For reverse osmosis (RO) sample collection, the reverseosmosis system is turned on and flushed for a predetermined amount oftime to initiate production of reverse osmosis water. Then the user isprompted to collect the sample by tapping into this flow.

FIG. 77 shows an exemplary implementation of the Take Samplesapplication. The Evaluate Dialysate Sample state 7702 of the TakeSamples application 7701 determines whether a dialysate sample isscheduled. The Start Dialysate Sample state 7703 starts dialysate flow,allowing the patient to take a sample. The Evaluate RO Sample state 7704determines whether a reverse osmosis sample is scheduled. The Start ROProduction state 7705 starts RO production in preparation for an ROsample. A timer may allow the reverse osmosis membrane to be adequatelyflushed such that water quality is acceptable. The Collect RO Samplestate 7706 allows the patient to collect an RO Sample.

(11) Replace Components

The Replace Components application gives the user the ability to replacecertain components when they have reached the end of their life. FIG. 78shows an exemplary implementation of the Replace Components application.

The Requesting Component Replacement state 7802 of the application 7801shows which components should be replaced and allows the user to requestadditional replacements. The Deprime Flow path state 7803 decides which,if any, part of the machine needs to be deprimed. The Evaluating BloodSide Drain state 7804 determines if the blood side needs to be drained.It evaluates the different ways in which the dialyzer and blood tubingset could require replacement. If the dialyzer and blood tubing set needto be changed, but are not clotted off, then the state may request thatthey be drained of fluid. The Evaluating Dialysate Side Drain state 7805determines if the dialysate side needs to be drained. It evaluates thedifferent ways in which the dialysate-side components could requirereplacement; if so, then the state will request they be drained offluid. The Empty Dialysate Tank state 7806 removes any residualdialysate or reverse osmosis water from the dialysate tank by sending itto drain. When the Empty Tanks command has completed, the event TankEmpty 7807 is emitted. The Draining Dialysate Side state 7808 removesfluid from the ultrafilter.

The Evaluating Dialyzer Replacement state 7809 determines whether thedialyzer and blood tubing set require replacement. The ReplacingDialyzer state 7810 steps the patient through dialyzer (and blood tubingset) replacement. For example, directions for replacing the dialyzer maybe displayed. When the user indicates the dialyzer has been replaced,the Dialyzer Replaced event may be emitted. The Evaluating UltrafilterReplacement state 7811 determines if the ultrafilter requiresreplacement. The Replacing Ultrafilter state 7812 steps the patientthrough ultrafilter replacement. The Replacing Drain Cassette state 7813steps the patient through ultrafilter replacement. For example,directions for replacing the drain cassette may be displayed. When theuser indicates the drain cassette has been replaced, a Drain CassetteReplaced event 7814 may be emitted. The Evaluating Dialysate CartridgeReplacement state 7815 determines if the Dialysate Cartridge requiresreplacement. For example, directions for replacing the dialysatecartridge may be displayed. When the user has indicated they havecompleted replacement, the Components Replaced event 7816 may beemitted.

The Evaluating Dialyzer Connections state 7817 determines whether thedialyzer and blood tubing set connections require testing. The CheckingDialyzer state 7818 may ensure that the dialyzer has been replacedcorrectly and that there are no leaking connections. If the dialyzercheck is okay, the Dialyzer Check Okay event 7819 may be emitted. TheFixing Dialyzer Connections state 7820 allows the patient to correct amisplaced connection. For example, instructions for fixing the dialyzerconnection may be displayed. The Evaluating Ultrafilter Connectionsstate 7821 determines whether the dialyzer and blood tubing setconnections require testing. The Fixing Ultrafilter Connections state7822 allows the patient to correct a misplaced connection. For example,instructions for fixing the ultrafilter connection may be displayed. Ifthe ultrafilter check 7823 is okay, the Ultrafilter Check Okay event7824 is emitted. The Evaluating Drain Cassette Connections state 7825determines whether the drain cassette connections require testing. TheFixing Drain Connections 7826 state allows the patient to correct amisplaced connection. Instructions for fixing the drain cassetteconnections may be displayed. The Checking Dialysate Cartridge state7827 ensures the dialysate cartridge has been replaced correctly andthat there are no leaking connections. If the dialysate cartridge checkis okay, the Connections Checked event 7828 may be emitted. The FixingDialysate Cartridge Connections state 7829 allows the patient to correcta misplaced connection.

(12) Install Chemicals

The Install Chemicals application allows the user to install chemicalconcentrates in preparation for dialysate production. Dialysate is madefrom chemical concentrates that are diluted with reverse osmosis water.The chemical concentrates are connected to the machine prior todialysate production, but not during recycling. The machine checks theconnection of the chemical concentrates following their installation. Inthe case that the chemical concentrates are not properly connected tothe machine, the user will have the opportunity to correct thesituation.

FIGS. 79 a and 79 b show an exemplary implementation of the InstallChemicals application. The Active state 7902 of the application 7901 isthe state in which Install Chemicals processing occurs. The stategenerates the event Install Chemicals Stopped 7903 on transitioning tothe Idle state 7904.

Referring to FIG. 79 b , the Install new Concentrates state 7905 promptsthe user to replace the chemical concentrate container. The EnsureConnection test 7906 detects whether the chemicals have been installedproperly in the system. The Connection Recovery state 7907 handles theuser interaction in the event that the system detects that the chemicalconcentrates are not installed properly. The system may notify the userto verify that the chemicals are properly installed and all connectionare securely fastened. The Dilute Chemicals state 7908 fills thechemical bags with water to dilute the chemicals. The Start DialysateProduction state 7909 is responsible for starting Dialysate production.

The Dialysate Leak Alarm state 7910 will stop Operation and notify theuser a dialysate leak has been detected. The Leak Resolution state 7911waits for the user to clear the leak, and for an indication from theuser of the same.

Referring again to FIG. 79 a , the Data Handler Init state 7912 isresponsible for initializing the data items for Install Chemicals. Oncompleting this initialization, it will generate a Install ChemicalsLaunch OK event 7913 to indicate that Install Chemicals is ready foractivation. The Update Data state 7914 is responsible for maintaining upto date values for the data items for Install Chemicals, such as thetreatment prescription and mix.

A number of features or attributes may be desirable in the hemodialysissystem embodiments described herein. These features or attributes mayrelate, for example, to automation, safety, usability, the userinterface, therapy programming, prescription data, patient entry data,summary data, and/or therapy display data. Exemplary features orattributes of the hemodialysis system embodiments are described below.Various features or attributes or combinations of such features orattributes may be incorporated in embodiments of the hemodialysissystems described herein. However, such features and attributes may notbe required by the system. Thus, while the features or attributesdescribed may be advantageously incorporated into one or morehemodialysis system embodiments in some circumstances, the hemodialysissystem need not include any of the described features or attributes, andthe system is not limited to the inclusion of any such features orattributes.

Exemplary features or attributes of the automation of the system will bedescribed first. Embodiments of the hemodialysis system described hereinmay be designed to permit the patient to operate the system and/or betreated from a standing, sitting and/or reclining position. As describedherein, the hemodialysis system may automatically perform a number offunctions, including: priming the blood set and dialysate pathways priorto treatment; rinsing and disinfecting; testing the integrity ofultrafilters and dialyzers; priming blood into the blood set, eitherthrough a prime returned or prime discarded operation; and rinsing backblood at the conclusion of a treatment. The hemodialysis system mayminimize the residual red blood cells in the blood set at the completionof rinseback, and may ensure that the per-treatment red cell loss isless than or equal to the per-treatment red cell loss for traditionalthrice weekly hemodialysis treatments. The hemodialysis system mayautomatically perform a solution infusion, upon request, at any timefrom the moment priming has started until rinseback is completed. Thetreatment device may automatically deliver heparin during treatment. Thehemodialysis system may automatically record patient blood pressure andweight. This may be accomplished through the use of wirelesscommunications with external, stand-alone sensor modules. Thehemodialysis system may confirm that components have been loadedcorrectly and that the correct and sufficient supplies (i.e. solutions,concentrates, etc.) have been connected. The hemodialysis system mayverify that the blood treatment set has been loaded correctly.

The hemodialysis system may comply with the FDA and AAMI guidelines ondialyzer reuse in testing and monitoring of the dialyzer's performance.The hemodialysis system may allow the patient to schedule their nexttreatment to reduce preparation time at the time of treatment. Thehemodialysis system may provide a feature to allow the user to safelydisconnect temporarily with a rinse back during treatment for 30 minutesor less. The hemodialysis system may provide the ability for theHealthcare Professional to disable the temporary disconnect feature. Thehemodialysis system may minimize therapy interruptions by preventing orattempting to self-resolve conditions that may lead to an interruption(i.e. an alarm).

Next, exemplary safety features and attributes will be described. Thehemodialysis may be designed to meet certain safety standards. Forexample, the hemodialysis system may meet all relevant AAMI and IECsafety requirements for hemodialysis machines, and may be designed suchthat exterior exposed surfaces stay below the levels indicated in theIEC-60601-1 standard during operation. Further, the user interface forthe dialysis system may certain safety control features. For example,the hemodialysis system may provide a mechanism for the patient toterminate a therapy and rinseback at any point during treatment.Further, a method for the patient to rinse back their blood even if anonrecoverable alarm occurs or power is lost may be provided. The usermay also be able to bring the instrument to a safe state (i.e. pause allinstrument activities) at any time during operation with a single buttonpress.

As described herein, air bubbles may be dangerous to a patient. Thus,the hemodialysis system may be constructed to prevent air bubbles sized20 microliters or larger from reaching the patient. The hemodialysissystem may trigger an alarm when streams of bubbles greater than orequal to 1 microliter accumulate to exceed 20 microliters total within30 sec. Further, the hemodialysis system may trigger an alarm whenstreams of bubbles greater than or equal to 3 microliters accumulate toexceed 20 microliters total within 30 sec.

The hemodialysis system may include a number of safety detectionfeatures. For example, the hemodialysis system may include, or interfaceto, a feature to detect venous needle dislodgement. The hemodialysissystem may detect the passage of blood across the dialyzer membrane. Thehemodialysis system may also detect and alert the user to dripping leaksfrom the portions of the blood circuit contained within the confines ofthe device. In addition, fluid in the blood circuit that the patient isexposed to may be of “dialysate for injection” quality.

The hemodialysis system may be designed to be usable to patients ofvarying physical and mental abilities. For example, the hemodialysissystem user interface may be compatible with dialysis operatorssuffering from retinopathy and neuropathy and readable by someone who iscolor blind. In particular, critical information displayed by the userinterface may be viewable from a distance of 3 feet by a user with 20/70vision, and non-critical information displayed by the user interface maybe viewable from a distance of 2 feet by a user with 20/70 vision. Thehemodialysis system user interface may be designed to be intuitive, sothat it may be understood by an operator with a 5th grade reading level.In addition, the hemodialysis system may be designed to be operatedone-handed, including during therapy. This assists patients who have onearm immobilized due to needles being present in the access site.

The user interface may also be designed to be flexible and functional.For example, the hemodialysis system user interface may be splash/spillresistant and cleanable with the following cleaning solutions withoutdegradation of operation: wiped 5.25% sodium hypochlorite bleach diluted1:10, wiped accelerated hydrogen peroxide (made by Virox Tech Inc), andwiped PDI Sani-Cloth Plus.

Illumination may be controllable by the user or based on certainfactors. For example, the hemodialysis system may be provided with amechanism to dim the user interface and minimize all other lightemissions either by request or automatically. In addition, it may bepossible to turn off all light emitting sources except those necessaryto locate safety-critical controls such as the stop button. In the eventof a power outage, illumination of the blood set and dialyzer may beprovided to support the patient managing their blood lines and access.The hemodialysis system may provide illumination to the appropriatecontrols when user interaction with the controls is necessary. Thisassists the user in finding necessary controls when performing therapyin a dark environment.

As discussed herein, alarms may be triggered during use of the dialysissystem. The hemodialysis system may provide audible and visualindication of alarm conditions. Further, the hemodialysis system maydistinguish the importance of an alarm condition. The audio abilities ofthe hemodialysis system may allow for a range of frequencies and soundlevels, e.g., for alarm and alert situations, which may be adjustable bya user. The hemodialysis system may provide the ability for the user tomute an alarm. The hemodialysis system may have a visual indicator, inaddition to the GUI, to call attention to alarms and alerts. Forexample, the hemodialysis system may generate a “light pole” or othersuch visual alarm indicator that can be viewed from a significantdistance in all directions (e.g., 20 feet).

The hemodialysis system GUI may explain possible causes of an alarm andwhether the alarm is correctable or not correctable. If an alarm iscorrectable, the hemodialysis system user interface may guide the userthrough resolving the alarm. The hemodialysis system may also provideinstructions on when to call service or a Healthcare Professional.

The user interface and labeling may support a number of differentlanguages and alternative character sets. Further, the hemodialysissystem may provide voice guidance in the supported languages. Wherepossible, connections may be keyed and color-coded to facilitate correctconnections.

The hemodialysis system user interface may provide the user with anoption to receive a notification at the end of treatment, and may allowthe user to review relevant treatment data at the end of the treatment.

It may be desirable that the hemodialysis system be easy to operate anduser friendly for non-professionals. The user interface and industrialdesign of the hemodialysis system may allow the device to look and feellike a home product, and have a simple interface. Operations to beperformed by a patient may be graphically simulated on-screen. Aproperly trained patient may be able to initiate treatment within 10minutes of requesting a therapy. The hemodialysis system user interfacemay be configurable into “novice” and “advanced” modes that helpencourage and guide novice users, while providing quick navigation foradvanced users.

The hemodialysis system may allow the user to recover from missteps andmistakes, for example through use of back navigation in the userinterface or an undo function. Further, the hemodialysis system userinterface may minimize the user time and effort required to obtain help.The hemodialysis system may provide Healthcare Professional-specifictraining manuals, patient-specific training manuals, and an operator'smanual.

The hemodialysis system may support Healthcare Professional localizationof the device consisting of setting the language for display of textelements, setting the time, and setting units for parameters (i.e. lbsor kgs). The hemodialysis system may support Healthcare Professionalconfiguration of the patient prescription, including setting thepatient's target weight, the allowable therapy configurations (i.e.short daily, extended treatment) and the associated blood flow rate, theflexibility to set either dialysate flow rate and time or the dialysatevolume and time for each therapy configuration (i.e. short daily,extended treatment), the prescribed heparin protocol, the maximumultrafiltration rate, the dialysate composition, the dialyzeridentification, solution infusion bolus size and limits, arterial andvenous pressure limits, rinseback volume, and prime method (prime returnor prime dump). The hemodialysis system may provide the option toprevent the patient adjustment of each prescription parameter andprovide maximum/minimum limits on patient adjustment of the prescriptionparameters.

The hemodialysis system may support manual and electronic input of thepatient prescription. The hemodialysis system may be designed tominimize the amount of information that is required to be manuallyentered for each therapy.

The device may require the patient to provide the following inputs atthe start of therapy: therapy type (e.g. short daily, extended duration)and pre-dialysis weight. Prior to and during therapy, the hemodialysissystem may allow the user to adjust the therapy end time. Thehemodialysis system may provide the ability for input of the sittingand/or standing patient blood pressure both prior to therapy and aftertherapy completion.

The device may display, for confirmation, the following calculatedparameters, at a minimum, on the summary screen prior to the start oftreatment: therapy duration/end time and the patient's end weight. Thehemodialysis system may allow the user to adjust the end weight for thetherapy prior to and during therapy. in addition, prior to and duringtherapy, the hemodialysis system may allow the user to adjust thetherapy end time/duration for the therapy.

Unless superseded by an alarm or user request, the hemodialysis systemmay always display the following information: current system state (i.e.priming, therapy, etc.), current blood flow rate, current patient weightand target patient weight, cumulative therapy time and therapy end time,and volume of heparin delivered. When using an associated blood pressuremonitor (cuff), the hemodialysis system may display a new blood pressuremeasurement for 5 minutes after that measurement was taken. Thehemodialysis system may display, on demand, real-time feedback on actualblood flow. This facilitates needle adjustment for optimal blood flow.On demand, the hemodialysis system may provide a means for the user toview the following information: dialysate conductivity and flow rate,the most recent blood pressure measurement, current ultrafiltrationremoval rate, cumulative bolus volume infused, dialysate temperature,current arterial and venous pump pressures, and the blood volumeprocessed.

The following are each incorporated herein by reference in theirentireties: U.S. Provisional Patent Application Ser. No. 60/903,582,filed Feb. 27, 2007, entitled “Hemodialysis System and Methods”; U.S.Provisional Patent Application Ser. No. 60/904,024, filed Feb. 27, 2007,entitled “Hemodialysis System and Methods”; U.S. patent application Ser.No. 11/787,213, filed Apr. 13, 2007, entitled “Heat Exchange Systems,Devices and Methods”; U.S. patent application Ser. No. 11/787,212, filedApr. 13, 2007, entitled “Fluid Pumping Systems, Devices and Methods”;U.S. patent application Ser. No. 11/787,112, filed Apr. 13, 2007,entitled “Thermal and Conductivity Sensing Systems, Devices andMethods”; U.S. patent application Ser. No. 11/871,680, filed Oct. 12,2007, entitled “Pumping Cassette”; U.S. patent application Ser. No.11/871,712, filed Oct. 12, 2007, entitled “Pumping Cassette”; U.S.patent application Ser. No. 11/871,787, filed Oct. 12, 2007, entitled“Pumping Cassette”; U.S. patent application Ser. No. 11/871,793, filedOct. 12, 2007, entitled “Pumping Cassette”; and U.S. patent applicationSer. No. 11/871,803, filed Oct. 12, 2007, entitled “Cassette SystemIntegrated Apparatus.” In addition, the following are incorporated byreference in their entireties: U.S. Pat. No. 4,808,161, issued Feb. 28,1989, entitled “Pressure-Measurement Flow Control System”; U.S. Pat. No.4,826,482, issued May 2, 1989, entitled “Enhanced Pressure MeasurementFlow Control System”; U.S. Pat. No. 4,976,162, issued Dec. 11, 1990,entitled “Enhanced Pressure Measurement Flow Control System”; U.S. Pat.No. 5,088,515, issued Feb. 18, 1992, entitled “Valve System withRemovable Fluid Interface”; and U.S. Pat. No. 5,350,357, issued Sep. 27,1994, entitled “Peritoneal Dialysis Systems Employing a LiquidDistribution and Pumping Cassette that Emulates Gravity Flow.” Alsoincorporated herein by reference are U.S. patent application Ser. No.12/038,474, entitled “Sensor Apparatus Systems, Devices and Methods,”filed on Feb. 27, 2008; U.S. patent application Ser. No. 12/038,648,entitled “Cassette System Integrated Apparatus,” filed on Feb. 27, 2008;and U.S. patent application Ser. No. 12/072,908, filed Feb. 27, 2008,entitled “Hemodialysis Systems and Methods.”

In addition, incorporated herein by reference in their entireties, andfiled on an even date herewith, are the following: U.S. patentapplication Ser. No. 12/198,947, entitled “Occluder for a MedicalInfusion System”; U.S. patent application Ser. No. 12/199,055, entitled“Enclosure for a Portable Hemodialysis System”; U.S. patent applicationSer. No. 12/199,062, entitled “Dialyzer Cartridge Mounting Arrangementfor a Hemodialysis System”; U.S. patent application Ser. No. 12/199,068,entitled “Modular Assembly for a Portable Hemodialysis System”; U.S.patent application Ser. No. 12/199,077, entitled “Blood Circuit Assemblyfor a Hemodialysis System”; U.S. patent application Ser. No. 12/199,166,entitled “Air Trap for a Medical Infusion Device”; U.S. patentapplication Ser. No. 12/199,176, entitled “Blood Line Connector for aMedical Infusion Device”; U.S. patent application Ser. No. 12/199,196,entitled “Reagent Supply for a Hemodialysis System”; and U.S. patentapplication Ser. No. 12/199,452, filed Aug. 27, 2008, and entitled“Hemodialysis System and Methods.”

While several embodiments of the present invention have been describedand illustrated herein, those of ordinary skill in the art will readilyenvision a variety of other means and/or structures for performing thefunctions and/or obtaining the results and/or one or more of theadvantages described herein, and each of such variations and/ormodifications is deemed to be within the scope of the present invention.More generally, those skilled in the art will readily appreciate thatall parameters, dimensions, materials, and configurations describedherein are meant to be exemplary and that the actual parameters,dimensions, materials, and/or configurations will depend upon thespecific application or applications for which the teachings of thepresent invention is/are used. Those skilled in the art will recognize,or be able to ascertain using no more than routine experimentation, manyequivalents to the specific embodiments of the invention describedherein. It is, therefore, to be understood that the foregoingembodiments are presented by way of example only and that, within thescope of the appended claims and equivalents thereto, the invention maybe practiced otherwise than as specifically described and claimed. Thepresent invention is directed to each individual feature, system,article, material, kit, and/or method described herein. In addition, anycombination of two or more such features, systems, articles, materials,kits, and/or methods, if such features, systems, articles, materials,kits, and/or methods are not mutually inconsistent, is included withinthe scope of the present invention.

All definitions, as defined and used herein, should be understood tocontrol over dictionary definitions, definitions in documentsincorporated by reference, and/or ordinary meanings of the definedterms.

The indefinite articles “a” and “an,” as used herein in thespecification and in the claims, unless clearly indicated to thecontrary, should be understood to mean “at least one.”

The phrase “and/or,” as used herein in the specification and in theclaims, should be understood to mean “either or both” of the elements soconjoined, i.e., elements that are conjunctively present in some casesand disjunctively present in other cases. Multiple elements listed with“and/or” should be construed in the same fashion, i.e., “one or more” ofthe elements so conjoined. Other elements may optionally be presentother than the elements specifically identified by the “and/or” clause,whether related or unrelated to those elements specifically identified.Thus, as a non-limiting example, a reference to “A and/or B”, when usedin conjunction with open-ended language such as “comprising” can refer,in one embodiment, to A only (optionally including elements other thanB); in another embodiment, to B only (optionally including elementsother than A); in yet another embodiment, to both A and B (optionallyincluding other elements); etc.

As used herein in the specification and in the claims, “or” should beunderstood to have the same meaning as “and/or” as defined above. Forexample, when separating items in a list, “or” or “and/or” shall beinterpreted as being inclusive, i.e., the inclusion of at least one, butalso including more than one, of a number or list of elements, and,optionally, additional unlisted items. Only terms clearly indicated tothe contrary, such as “only one of” or “exactly one of,” or, when usedin the claims, “consisting of,” will refer to the inclusion of exactlyone element of a number or list of elements. In general, the term “or”as used herein shall only be interpreted as indicating exclusivealternatives (i.e. “one or the other but not both”) when preceded byterms of exclusivity, such as “either,” “one of,” “only one of,” or“exactly one of.” “Consisting essentially of,” when used in the claims,shall have its ordinary meaning as used in the field of patent law.

As used herein in the specification and in the claims, the phrase “atleast one,” in reference to a list of one or more elements, should beunderstood to mean at least one element selected from any one or more ofthe elements in the list of elements, but not necessarily including atleast one of each and every element specifically listed within the listof elements and not excluding any combinations of elements in the listof elements. This definition also allows that elements may optionally bepresent other than the elements specifically identified within the listof elements to which the phrase “at least one” refers, whether relatedor unrelated to those elements specifically identified. Thus, as anon-limiting example, “at least one of A and B” (or, equivalently, “atleast one of A or B,” or, equivalently “at least one of A and/or B”) canrefer, in one embodiment, to at least one, optionally including morethan one, A, with no B present (and optionally including elements otherthan B); in another embodiment, to at least one, optionally includingmore than one, B, with no A present (and optionally including elementsother than A); in yet another embodiment, to at least one, optionallyincluding more than one, A, and at least one, optionally including morethan one, B (and optionally including other elements); etc.

It should also be understood that, unless clearly indicated to thecontrary, in any methods claimed herein that include more than one stepor act, the order of the steps or acts of the method is not necessarilylimited to the order in which the steps or acts of the method arerecited.

In the claims, as well as in the specification above, all transitionalphrases such as “comprising,” “including,” “carrying,” “having,”“containing,” “involving,” “holding,” “composed of,” and the like are tobe understood to be open-ended, i.e., to mean including but not limitedto. Only the transitional phrases “consisting of” and “consistingessentially of” shall be closed or semi-closed transitional phrases,respectively, as set forth in the United States Patent Office Manual ofPatent Examining Procedures, Section 2111.03.

What is claimed is: 1.-29. (canceled)
 30. A controller for ahemodialysis system, the hemodialysis system comprising actuators thatcooperate to perform dialysis functions and sensors that cooperate tomonitor dialysis functions, the controller comprising: a user interfacemodel layer configured to manage the state of a graphical user interfaceand receive inputs from a graphical user interface; a therapy layer,below the user interface model layer, configured to run state machinesthat generate therapy commands based at least in part on the inputs fromthe graphical user interface; and a machine layer, below the therapylayer, configured to provide commands for the actuators based on thetherapy commands, wherein the therapy layer is configured to receivecommand requests from the user interface model layer, wherein somecommands are state specific and other commands are valid in any state,wherein the therapy layer is configured to decide if the current commandrequest will be acted upon or not, and wherein the therapy layer isconfigured to reject the command request and to return to a user anappropriate reason for the rejection, if the current state is not validfor the command.
 31. The controller of claim 30, further comprising auser interface views layer, above the user interface model layer,configured to control the visual appearance of the graphical userinterface.
 32. The controller of claim 31, wherein the user interfacemodel layer is configured to provide to the user interface views layer acurrent screen state.
 33. The controller of claim 30, wherein thetherapy layer is further configured to verify the inputs from thegraphical user interface relative to information relating to expectedinputs.
 34. The controller of claim 30, wherein the therapy layer isconfigured to provide to the user interface model layer a status of thetherapy.
 35. The controller of claim 30, wherein the machine layer isconfigured to provide to the therapy layer an indication of theintegrity of the actuators.
 36. The controller of claim 30, wherein themachine layer is configured to provide to the therapy layer data sensedby the sensors.